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Send us a textToday Vanessa & Heather discuss what POMC is, and how it supports our health! POMC is the central hub of metabolic and hormonal balance. This health supportive protein production of POMC is stimulated by leptin and UV light and results in nine bio-active peptides each with major health-promoting benefits. We are told to avoid UV light, but it stimulates the production of POMC and ALL its incredible healing power! Don't miss this powerful episode! If you want to learn how to use sunlight as medicine safely grab the, Get Your Light Right Webinar & Ebook https://brightlightwellnesscoach.com/light-right-webinarSupport the showFind Heather:https://www.instagram.com/heathercrimson/https://www.enlightenedmood.comDiscount codes:https://www.vivarays.com ➡️ Code: enlightenedmood.com for 10% offhttps://midwestredlighttherapy.com ➡️ Code: enlightenedmood for 10% offhttps://emr-tek.com ➡️ Code: enlightenedmood for 20% offFind Vanessa:https://instagram.com/bright_light_wellness/vanessabaldwin/https://www.instagram.com/healingfamilieswithhomeopathy/Website: https://brightlightwellnesscoach.com/Discount codes:https://midwestredlighttherapy.com/ ➡️ Code: Brightlightwellnesshttps://vivarays.com/ ➡️ Code: BrightlightwellnessFree Product Guide http://gem.godaddy.com/signups/3cdbe47a101a4d2d9b991e9b5c9a981e/join Free Homeopathy Guide ...
Send us a textShort Summary: The science of obesity and appetite regulation, blending genetics and neurobiology with practical insightsAbout the guest: Giles Yeo, PhD is a professor of molecular neuroendocrinology at the University of Cambridge. He leads a lab studying obesity and appetite regulation.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.Episode Summary: Nick interviews Dr. Giles Yeo about the genetics and neurobiology of obesity, starting with the discovery of leptin in the obese mouse model, detailing its role in appetite regulation via the hypothalamus, and discussing GLP-1 drugs like Ozempic for weight loss. It delves into how genetic factors, like the leptin-melanocortin pathway, influence hunger, the heritability of body weight, and societal factors driving the obesity epidemic, emphasizing the interplay of biology and environment.Key Takeaways:Leptin, discovered through the obese mouse, signals fat levels to the brain, but its absence causes severe obesity and infertility, as seen in rare human mutations.The hypothalamus, a key brain region, senses hormones like leptin and GLP-1, balancing hunger and satiety through POMC (anorexigenic) and AgRP (orexigenic) neurons.Body weight heritability is 40-70% at the population level, but this does not mean that 40-70% of someone's body fat composition is due to genetic factors outside human control. Dr. Yeo unpacks how to think about it.GLP-1 drugs (e.g., Ozempic) mimic gut hormones to reduce appetite, offering some people 15-25% weight loss, but require long-term safety monitoring.According to Dr. Yeo, obesity reflects energy imbalance, but nutritional density matters more than calorie counting for health, and societal changes are needed to prevent it.Related episode:M&M #132: Obesity Epidemic, Diet, Metabolism, Saturated Fat vs. PUFAs, Energy Expenditure, Weight Gain & FeediSupport the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Use code MIND for 10% off. Readwise: Organize and share what you read. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off. For all the ways you can support my efforts
Have you ever finished a huge meal but still found room for dessert? Some people might talk about having a separate stomach for desserts. It turns out that your brain might be driving you to eat that sweet treat even though you don't 'need' it. Recent research in the journal Science found that the same nerve cells that signal 'you're full' also spark cravings for you wanting something sweet. Deep within a part of your brain called the hypothalamus are special cells known as pro-opiomelanocortin (POMC) neurons. They are well known for their role in telling us when we're full - however, these neurons have been found to have a surprising double life. When sugar enters your mouth, POMC neurons release natural opioids, like ß-endorphin, which trigger a rewarding sensation making us want more of the sugar even if our stomach is already full. The researchers found this out using experiments on mice. First, they bathed slices of mouse brain tissue in a fluorescent solution that binds to opioid receptors. They found that the highest density of these receptors was in a brain region known as the PVT, a key player in regulating feeding behaviours. This hinted at a direct link between the fullness signal and sugar cravings. They then let some lab mice eat their regular meal. After about 90 minutes, when the mice were clearly full, introduced a dessert of sugary food. Neuronal activity between the arcuate nucleus and the PVT spiked to nearly four times the level observed during the meal. Interestingly, this surge began before the mice even started eating the dessert, suggesting that the brain anticipates the sweet treat. To confirm this pathway, the scientists used a technique called optogenetics which uses light to control cells. When they inhibited the signals from the POMC neurons to the PVT, the mice consumed 40 percent less dessert. This confirmed that these satiety neurons, far from solely curbing appetite, also drive our desire for sugar when we're full. The researchers hypothesise that this might be evolutionary. Sugar was once a rare and quick source of energy and our brains evolved to seize opportunities when they come around, which may have meant eating more energy rich foods when you're already full. While sugar is now plentiful, that ancient wiring could still make us crave a sweet finish to our meals. Understanding that our dessert cravings have a neurological basis might help pave the way for new approaches to combat overeating and obesity. By targeting the specific brain pathways that drive sugar cravings, future treatments could help reduce excessive sugar consumption without dampening overall appetite. Next time you're tempted by that slice of cake after dinner, remember: it's not just a sweet tooth, it's your brain's finely tuned system working as it has for millennia. LISTEN ABOVESee omnystudio.com/listener for privacy information.
In this episode, we have on Zaid Dahhaj, who emphasizes the power of sunlight and circadian biology. Zaid shares insights on circadian disruption, especially as a new parent navigating sleep patterns with his one-year-old. We unpack misconceptions around UV light and skin health, discussing the intricate relationship between exercise timing and circadian rhythms, as well as the impact of artificial light and wearables on your long term health. If you're looking to enhance your health through a fresh lens, tune in for an enlightening conversation filled with practical tips and engaging discussions! Timestamps: 00:00:00 - Introduction 00:05:30 - Zaid's backstory 00:08:54 - Explaining Circadian Biology to clients 00:09:56 - “It's too simple to be true” 00:11:24 - Overcoming mental blocks 00:12:28 - Sun damage and the NIvea Scan 00:15:07 - Preparing for sun exposure 00:17:19 - Debating with dermatologists 00:19:13 - Misconceptions about sunlight 00:20:40 - Melanoma 00:22:08 - Fasting and keto 00:23:46 - “What I Eat In A Day” 00:26:35 - Food noise, peptides, and POMC 00:29:40 - Blue light blockers and sleep quality 00:33:49 - Artificial light and your health 00:36:45 - Staying in shape 00:38:43 - Optimizing your workout routine 00:43:05 - Circadian biology and exercise 00:46:19 - Parenting and sleep hygiene 00:49:12 - Circadian parenting tips 00:54:03 - Centralized medicine 00:58:08 - Airpods, Apple Watches, and EMF 01:01:31 - Hearing health 01:03:50 - Skepticism and scientific data 01:05:21 - Sleep hygiene tips and boundaries with technologies 01:07:59 - Everyone is on their own journey 01:09:25 - Educating the masses 01:15:27 - Where to find Zaid Sponsored By: Paleo Valley Go to http://paleovalley.com/sarahk and use code SarahK for 15% off Upgraded Formulas: Use code: YOGI for 10% off at www.upgradedformulas.com Viva Rays Go to vivarays.com & use code: YOGI to save 15% Check Out Zaid: Substack Website Instagram Twitter Podcast This video is not medical advice & as a supporter to you and your health journey - I encourage you to monitor your labs and work with a professional! ________________________________________ Get all my free guides and product recommendations to get started on your journey! https://www.sarahkleinerwellness.com/all-free-resources Check out all my courses to understand how to improve your mitochondrial health & experience long lasting health! (Use code PODCAST to save 10%) - https://www.sarahkleinerwellness.com/courses Sign up for my newsletter to get special offers in the future! -https://www.sarahkleinerwellness.com/contact Free Guide to Building your perfect quantum day (start here) - https://www.sarahkleinerwellness.com/opt-in-9d5f6918-77a8-40d7-bedf-93ca2ec8387f My free product guide with all product recommendations and discount codes: https://www.sarahkleinerwellness.com/resource_redirect/downloads/file-uploads/sites/2147573344/themes/2150788813/downloads/84c82fa-f201-42eb-5466-0524b41f6b18_2024_SKW_Affiliate_Guide_1_.pdf
In this episode, Michael Frampton catches up with renowned surfer and coach Matt Grainger to talk about the highs and lows of surfing, the challenges of big waves, and the innovations in the sport. Matt shares his experiences with heavy waves, gnarly wipeouts, and the current state of surfing on the Sydney Northern Beaches. The discussion dives into the recent swells, the changing conditions, and how they impact surfers of all levels.Matt also discusses his latest project, the "Surfer's Compass" app, a comprehensive guide for surfers to improve their techniques, mindset, and fitness. He shares the inspiration behind the app, the process of its development, and the exciting features that it will offer. Episode Highlights:Matt's Recent Surf Trip to Indonesia: Matt shares the story of his recent trip to Indonesia, where he suffered a significant head injury after a day of surfing at Macaronis. He details the moment the injury occurred, the aftermath, and the crucial steps taken to avoid infection.The Importance of Surf Safety: Despite years of experience, Matt explains how ego and overconfidence led to a dangerous situation. He emphasizes the importance of wearing a helmet in heavy conditions and the risks of surfing over shallow reefs.Injury Management and Recovery: Matt provides valuable insights into managing injuries in remote locations, including the use of bottled water, antibiotics, and proper wound care to prevent infections from coral cuts.Mobility and Strength Training for Surfers: As a coach, Matt discusses the significance of maintaining mobility and strength as surfers age. He highlights the role of a balanced training program in injury prevention and long-term surfing performance.Mindset and Longevity in Surfing: Matt touches on the importance of a positive mindset, quoting Bruce Lee on the power of words and how they influence our physical and mental well-being. He encourages surfers to stay active, eat well, and maintain a youthful outlook to continue enjoying the sport well into their later years..Surf Culture Evolution: The changes in surfing culture, including the influx of new surfers and the impact on traditional breaks."Surfer's Compass" App: Insight into Matt's development of this app, aimed at improving surfing techniques, fitness, and mental strategies.For more insights and tips from Matt Grainger:Follow Matt Grainger:Instagram: mattgraingersurf.Linkedin:: Matt GraingeFollow Michael John Frampton:Instagram: @surfmasteryWebsite: https://surfmastery.com/.Full Show Transcript:[00:00:00] Matt Grainger: I think so. You look at all the surfers now. It's all legs. Hardly any upper body. Only back and legs. You don't want any chest, and you don't want to overload the shoulders as well in your rotator cuff. Exercises are really good. So light weights on the shoulders, nothing heavy. So you can still get that mobility in your padel. And you've got the power for your back for your paddle. So a lot of the strength training is like just Olympic rings, pull ups, maybe some skin. The cat. Um, um, dumbbell pull ups as well off the bench, all that kind of stuff. And then a lot of, a lot of, um, obviously squats with the. [00:00:40] Michael Frampton: Back to the Surf Mastery podcast. I am your host, Michael Frampton, and the ethos of this show is education and inspiration for better surfing and a better surfing life. And Matt Grainger, today's guest, not only was a huge part in the inspiration for the birth of this show, but he epitomizes that ethos as well. He is in his mid 50s now, and he's still out there surfing a ton and stays fit and healthy for surfing, and also teaches others to be better surfers and better people through better surfing mindset, health and fitness, etc. Matt is just a pure inspiration in the surfing world and just an absolute frother and a rips. He rips. He's an incredible surfer and stoked to get him back on the show. And like I said, he first appeared back in episode number one. He's. This will be his fourth appearance. Uh, he also appeared in episode 30 and episode 55 as well. And, uh, without further ado, I shall fade in my conversation. My fourth conversation on this podcast with Matt Grainger from Manly Surf School. How did it happen? Was it just a freak random thing, or was it a lapse in concentration or what? [00:02:07] Matt Grainger: Yeah, it was a bit of the ego took over and ego took over. Um, we'd had. Every day was the best day ever. We had this the first swell in June. And, um, this one day just got bigger and bigger, and it had a lot of south in it. There was two swells. It was like a south swell and a bit of south west as well. So you could get a chip in, you could chip in from behind, behind the tower, and you could backdoor where you'd usually take off. So you'd get like more barrel time. And I was riding this magic six zero Psi Pro, one that I've had for about a year. Felt unreal under my feet. Been riding it for days straight. And then, um, this guy Sean came out from South Africa. He rocked up on a boat. Him and I started paddling up the reef and just trading wave after wave and making him. So just making these unbelievable tubes and no one came up there because, you know, it was pretty gnarly. So if you fell, it was like two foot deep and it was like an eight foot swell. So when Max, probably 8 to 10, you probably saw footage of Nathan Florence. I don't know if you saw some of the footage of him and he's it was like 10 to 12 foot hits that day, whereas Max doesn't get bigger, it just gets thicker. So it's probably 6 to 8 foot, but really thick, like a chokes kind of way. You get this, you can make this really nice drop and then come in with speed. [00:03:28] Matt Grainger: And just if you made it, you're fine. But if you didn't make it, that's what happened. So after five hours, I actually wasn't even tired. I was after like five hours, I was just just getting cocky and I probably should have gone in. It was more like one more, one more. And Shaun and I were trying to outdo each other, and he he actually snapped his board, his board on his last wave, and I snapped my head, but I took off, made. It made. The drop. Drop was on the foam ball. As I was pumping on the foam ball, the wave turned the corner. So kind of that south west angle of the way though, turned a massive corner. So I've just got catapulted on the foam ball and I got thrown out head first, and that's as soon as my head landed, the lip hit the back of my neck and just drove me straight into the reef, like, instantly. It was only like two foot deep. It was low tide and I just it was just like, bang. I was like, no, I got a bit on here. And then I went into worry, went into warrior mode. You know, when you when I'd said us the way, way my eyes. Okay. It's actually got a cut there as well. So I've got to cut. I got cut either side. I got cuts either side of the nose down here on the bottom of the nose as well on this eye. [00:04:43] Matt Grainger: And obviously here I have about 25 stitches here, five stitches here. And I just went I knew the session was over and I just paddled back. Everyone was like, we'll get a boat. Everyone's screaming, get a boat, get a boat! That's it. I'm like, I'm good, I'm good. Getting myself back almost on my own. You know, like one guy got scared. Good on ya. Um, this guy Hans from America. He goes, good on you, tough guy. I'm like, nah, I've got this, I got this. Anyway. So I went back and got on the pontoon and just started pouring bottled water over my head. And then I got the boat back to Max and then looked for Shaz, and she was already stitching up my brother. He had a little cut on his back. So. And then someone said,, Matt's looking for you. Cut his head and neck. And she thought,, if he's asking for something, he's in a bad way. So then she saw my head and she thought I'd cracked. I'd actually, like, fractured my skull, but it was actually bits of coral coming out of my head. .Far out. So she pulled that, pulled the bits of coral out. He got some local, which was good. We'll just put it in the carts and then pulling bits of coral out the tweezers, and then got a toothbrush for an hour and just scrubbing it. That was the gnarly part. I just had to. [00:06:01] Michael Frampton: Scrubbing and all this peroxide or iodine or something. Yeah. [00:06:04] Matt Grainger: With, um. Yeah. Just with, um. Yeah. Like light alcohol. Yeah. Just. And just so you don't kill the flesh too much. Like, not too gnarly. Um, but just getting it all out, and that's. I reckon that saved me for sure. And then obviously took about two hours to stitch up, which was gnarly. And I was just doing I've been doing a lot of breath training like coaching, apnea training. And I saw resonance breathing, which is like a second inhale six second exhale. . So just going into that just and that helped big time. That was like a three hour ordeal which could have been a long time. Felt like a long time. But it wasn't as long as I thought. And then she put like a face mask over it so I couldn't see. And then, um, yeah, The rest is history. And then I surfed the next day., you did not. Yeah I know. He taped it up. I just said, I'll get two. I'll get one. Wait, I'll get one wave. And I did some tests, like I was jumping on one leg to see if I had concussion and then, no, I'm not well in the head anyway, uh, and then I came. I wore a helmet, of course, and then I didn't surf for after that day. I didn't surf for three and a half days. And then after that I was good to go because I was on. [00:07:21] Matt Grainger: I was having, uh, four courses of antibiotics. I four, four tablets of antibiotics every day, washing it with, um, fresh water. And we're getting she was breaking up antibiotics and putting it inside the cup as well. Yeah. And she and she left a little bit of one of the gnarly cuts. Didn't do it too tight. So bits of coral would still come out if it did. There's still little bits popping out, far out. But yeah. So I'm wearing a helmet from now on when it's gnarly like that. So I went to G-land. After that we had another swell at Max and Surf Greenbush, but I had one of those soft shell helmets that Tommy Scott wears. Yeah. By, um, DMC. It's like a rugby helmet. Yeah, yeah, but they're nice and light, but they're, um. Yeah. So that that felt good. And then I wore it in g-land every surf even because I didn't want to get hit and break the cuts open anymore. Yeah, yeah, yeah. I got the stitches out after six days and they healed well. Yeah. So wow. But from now on I'm going to. If it's gnarly and low tide and heavy, I'll be wearing a helmet. Yeah. No. Fair enough. But I was lucky I didn't get concussion and brain damage or lose an eye or nose or whatever. Yeah., yeah. [00:08:32] Michael Frampton: And I mean, and any sort of coral cut infection is such a huge risk, right? [00:08:38] Matt Grainger: I reckon like, even there was a girl, it was actually a girl out in the water. She. Her name's Kat. She does immense heavy new for about six months with a with harm. So her partner and they they had a long boat with um with a solar panel on top and just go around the islands and she, she had a cut on her foot. She went to seek a cut and just had a shower. So that got that sort of told. And she told me this story like a week before. And then she got this, this flesh eating, um, microbe in her foot. And she basically went delirious and had to go to she went to Padang and their hospital was too dirty and gnarly. So the hands got her out of there, carried her onto the fast ferry, then went to Jakarta and she had like three skin grafts and then back to LA. Yeah, just from that. So that straight away I was like, I'm not getting my head touching any, any, um, any shower water. So I was just it sounds very first world, but I was just every time I wash my head, I was just with bottled water. Yeah. Yeah. So that's a good tip for people out there. yeah. Yeah. Look after your carts. Yeah. Always look after my carts. Even feet. You know, I went to Chofu. First time I went to Chofu in 2000. A tiny little cuts on my feet. And it was the last day. And I was like, last day, who cares? And then I got home and I got stacked. I couldn't walk. I went to my. I went to my glands. And straight away I was on antibiotics and prednisone and it went away. But that was nasty. So it taught me a good lesson. Yeah. So get on, get on to your rep cards quickly people when you go to the tropics. [00:10:17] Michael Frampton: Yeah. You got to clean them eh. I remember I touched the reef in Arugam Bay in Sri Lanka once. Like just got this tiny little graze. Thought nothing of it. Just put like a little bit of iodine cream on it. That's all I did. And then two days later, it's just like 50 cent welt that's throbbing. [00:10:33] Matt Grainger: And I had to hit. [00:10:35] Michael Frampton: Yeah. Had to get some antibiotics. So should have just scrubbed it out with a toothbrush and done the right thing at the time. But it was such a small cut, you thought nothing of it. But they must have just been little bits of coral in there or something. [00:10:47] Matt Grainger: Yeah, yeah, that was one of the ones where the feeder chirps. Tiny little, like little nicks. Yeah. So, yeah, to get that tape. Yeah. So the tip from Shaz. Doctor. Shaz, my partner. Get. Take her. I always have, like, a spare toothbrush. That's clean. You can't even get it from that. If you get it from the hotel. But you never brush your teeth with it, so it's totally clean. And just scrub it. Scrub it. Um, use the little wipes. The the iodine alcohol wipes. So you do one offs and not nothing else dirty. And then just keep checking it. Yeah. And there's that. There's that tayo gin. That's pretty good from Indo. You know that Chinese, that red bottle. That's always cool. That Chinese. It's called tayo gin or the ayam. They don't use cream. She said use because it just festers in the tropics. Use the powder. The powder? Yeah. The powders of the guy. Yeah. Okay. So that's a go and then cover them up. Yeah. If you do your feet too. I always wear shoes. People give me heaps of crap in Indo because I'm always wearing. If I've got cuts, I'll put shoes on because you're walking around. You get dirt in the cuts. Yeah. So it's important if we always forget especially. Yeah. You're like, oh nah, I'll be right. Or, you know, you see so many guys just get smashed and don't even do anything. Yeah. [00:12:03] Michael Frampton:yeah. It's not worth the risk. I used to you're still out charging, catching heaps of waves. [00:12:07] Matt Grainger: Yeah, still surfing a lot. Um, pretty much surf every day. Sometimes twice. Um, got the gym. Surfer's gym. Which is good. That keeps me fit and healthy. They working on the mobility that you taught me years ago, and. Yeah, just building on that. I think that's a big key is mobility. As we get older and even the younger athletes that we coach too. I've got some pros that train at our gym and and we've got them on a mobility program. Whereas strength training and I found lately like in the last few years, like having the ability and also the strength training is huge just for reducing, reducing injury, keeping strong. Like I'm 55 this month. I don't even talk about your age too. It's really important what you say out of your mouth. You know there's a, there's a quote by Bruce Lee is like be careful what you say with your words because that's why it's called spells and spelling. Like you're saying, you hear heaps of guys walk around and go, I'm done. I'm old, I'm an old man and all this. And you're like, hey, mate. Like, no, it's all relative. Like it's it's you know what? It's time. Really anyway. You know, like just this thing we've made up, but, you know, there's biological age. And if you keep yourself fit and healthy and moving and eat well, sleep well. You can keep keep rocking till you're in your 80s, I reckon. [00:13:29] Michael Frampton: Yeah, man, I was just reading. Listening to a book, actually, about all of that. And this Harvard professor did an experiment where she got a bunch of 80 year old men, and she put them in a house where everything in the house was as if it was 30 years ago, and they were only allowed. So the TV programs, the books, the furniture, and they were only allowed to talk, talk about things as if it was 30 years ago in the present. And within a few days, their eyesight improved. Health, like blood pressure, improved everything just by just like placebo. Like extreme placebo effect. Wow. [00:14:11] Matt Grainger: That's awesome. Yeah, it's rare to get that book. [00:14:14] Michael Frampton: It's a rare book. I'll. I'll forward it to you and I'll put it in the show notes for listeners, too. I think it's called the mind body Connection or something. I'll put it in the show notes and I'll send it to you. [00:14:23] Matt Grainger: And even when I was at, um, not trying to name drop here, but when I was at Nazaré, I came in, I totally led back to the harbor because he broke down. It's quite funny. Like it was a big day. Like 60 foot. Perfect. Nazaré. And I was with Lucas Pereira, who's from Mavericks, who trains with me. He was towing with me on that. We were just shifting partners all day. And then I said, you lead like I don't even know lead any way from then. And I said, you make leads out to sea doing nothing. We should go check on him. And he's like, yeah, right. So we hammered out the lead and he goes, yeah, I ran out of fuel, guys. And you're like, why? He goes, I was having too much fun. You know, every time the beeper light came on the warning signal that was low on fuel, I just turned it off. And because it was a really good day and it was a really good Nazaré, like, clean 60 foot faces and whatnot. Anyway, so I, we hooked up my ski to his ski and towed him back to the harbor. And we got back to the, um, got back to the wharf, and I was just chatting to him about how we've got a gym and I've been following what he does working XPT programs, and I do a lot of breathwork, but I really like breathwork. [00:15:36] Matt Grainger: And and I said, yeah, yeah, we don't we don't talk about age, you know, in our gym because what you said the word, don't you ever say that word in front of me again. And he got really gnarly. And I was like, okay, man, settle down. And um, so it's there's a lot of truth to it. Hey, I see, like, Chaz is, um, she's my wife. She's over 60, and she's getting better because she only started 20 years. And there's guys at the beaches that used to rip when they were 20, and they've given up at 50, or probably given up at 50 because it's in their mindset., my knees and stuff and my back stuff. And you're like, well, what do you do about it? Do you um, do you do any mobility or you know, what are you eating? What are you how are you sleeping? Or you know, I don't know. They're like, I don't know, you just like, okay. So yeah, it's funny isn't it? And I think I think we were lucky our age like we've, we've been introduced to a lot of stuff. And if you're curious about it, which you are and I am, there's so much stuff you can learn going down that rabbit holes. [00:16:41] Michael Frampton: yeah. It's never ending. Kind of. [00:16:42] Matt Grainger: Ten. The crew ten years before us, probably a lot of them missed out on that eating poor food, poor movement. Um, yeah, I think it's good. I've got the hoop. I've had the hoop for, like, uh, probably five years now. I find that's really good because I'm. I'm really diligent about my sleep. It can be gnarly some days, and it gives you a bad sleep score. You've got to kind of let that go, and not even your day is ruined. Because I know some athletes who will like that, and they're like, I had to get rid of it because it said I had a bad sleep score and I'd have a bad day. I'm like, no, no, you got to get past that. But sleep is huge. Hey, like and probably read that book by Matthew Walker that was, you know, everyone knew how important sleep was. You know, we cure cancer and all sorts of ailments. Balance. Yeah. So yeah, they'll always I try to have a little nap in the Arvo if I get time. Yeah. Try to have a nap every Arvo. And I think it's good to have a nap if I have the luxury, because you're just not talking. You're not thinking. You're just having a little break from the world and then back into it. Have a training session at the gym with the crew and then dinner in bed again. So that's my little routine. Yeah. And not being and not used to have to always wake up super early or to plan that I ought to be up early and out there for stuff. But if now if the waves aren't that good, I'm not going to get up early just to punish myself for the early just for the sake of being the first guy out there. So now, because I've found on the sleep on your sleep scores, when you do actually sleep that extra hour in the morning. Yeah. You get a lot of benefits. It's crazy. And if you do go to bed early. Yeah. Mm. [00:18:18] Michael Frampton: Does does is surfing the main motivator for you to stay fit and healthy? [00:18:23] Matt Grainger: Yeah. For sure. Yeah, definitely. Yeah. Like I couldn't give a stuff like what I look like. I just want to actually be able to catch waves and still be able to surf. My brother and I just went to Macaronis together and we were both chatting that we probably surf better now than we were in our mid 20s, just because the boards are better. We've got more knowledge and we've kept our bodies good. Yeah. Yeah. So we've had no we've had no serious accidents though which is lucky. you know obviously head knocks and all that kind of stuff but nothing like haven't broken any major bones like bony broken hands and a few things like that, but not, you know, haven't broken a femur or anything, you know. So some guys obviously are disadvantaged if they have a major injury but haven't had any major injuries. And then now I've realized I used to always think when I was have had a niggle like a, like a niggling hip or, you know, you had to go to the chiropractor and you had to do this, you had to do and now you can kind of push through it and move through it. [00:19:24] Matt Grainger: I found that like. And if it's really serious, obviously go and see a physician, which is good. and you can get a really good massage or just to break that tissue down. But I found now you can move through pain and throughout the whole day like not, you know, everyone thinks, I've got to train for an hour and that's it. So I don't do it. You know, you can do little snacks like ten minutes here, you know, ten minutes in the morning, another ten minutes at lunchtime, another two minutes here, and then another two minutes and eventually kind of work through it. I remember when we were working together, you were pretty onto that early in the early days. Good diets. I love I like got into my fasting, which is good pretty much two meals a day. Love the bone broth. I'm doing a coffee, obviously. Black coffee, a little bit of coconut oil. So, yeah, that's just all these little hacks that we're learning. Just helping along the way, I reckon. [00:20:21] Michael Frampton: Yeah, but you've got that motivation. You want to keep surfing, you want to keep going to Indo and that's what. Yeah. That's what get you. Okay. No I'm not going to have that donut. I'm going to and I'm going to go to bed early because I want to I want to go and get barreled at Indo like. [00:20:36] Matt Grainger: no, it's such a good motivator. Yeah. And and it's, it keeps you young. Yeah. It keeps you young and young in the head too. And looking at boards that, you know, I'm still riding shore boards and my short boards like a five, five, nine. And I've got A53 Bobby quad that I ride in the wave pool. Yeah. So I can still ride short boards. yeah. And just having that and and the boards have gotten so good. Now, you know, just the rockers and the things all the shapers. And I remember Mike, Michael Ho was talking with his son Mason. I saw in an interview that he said, oh, dad, why do you think you're ripping so much now? And he goes to the boards and Michael's like, doesn't care. You know, he just he doesn't have Instagram or Facebook. He's just surfing and I've I've seen Coco out in the water when she's in Indo or here and she said, yeah pops. Just he just the proper. So he's, he's, he's not thinking about how he's 60 and he's charging you know. Yeah he's right. He's got, he's got new blades and getting tubed out back door and ripping on the backside at Alma-Ata and things like that. But yeah, that's the motivation is surfing. Yeah. And it's, it's such a fun sport. And I just always say to people, it's a puzzle. [00:21:51] Matt Grainger: You know, you every time you go for a surf, you're trying to work out that puzzle. It doesn't matter if it's one foot onshore or it's 20 foot bommies or it's crazy tubes in Indo, you're still trying to figure out how you're going to paddle in. How are you going to get to your feet? How are you going to generate speed? Is it a straight down drop? Is it a knifing drop? Am I going to get in my front foot early? All these little things that just come into play from all those years of experience, and you're trying to work out that puzzle, and then it's one foot. You just want to go out and do one big turn on a one footer and you're happy. So that's what keeps me motivated. Some days, even if it's crap, I'll still go out for like three waves and just I'll get my three waves and go to work and train. And I've got the training to, I've got rid of the cardio. So I'm sort of not really doing the cardio so much now. It's just strength and movement because if you do a good movement flow, you can get good cardio from that anyway. Yeah, I forgot my heart rate monitor and you're actually getting flexi, whereas you don't want to get stiff and then just doing the right strength training. [00:22:53] Matt Grainger: So you look at all the surfers now it's all legs, hardly any upper body, only back and legs. You don't want any chest and you don't want to overload the shoulders as well in your you know, the rotator cuff exercises are really good. So light weights on the shoulders, nothing heavy. So you can still get that mobility in your paddle. And you've got the power through your back for your paddle. So a lot of the strength training is like just Olympic rings, pull ups, maybe some skin. The cat. yeah. dumbbell pull ups as well, off the bench, all that kind of stuff. And then a lot of, a lot of,, obviously squats with the barbell, goblet squats, front squats, split squats, all that kind of stuff. It's super important, I reckon. So getting that mobility and doing the weights and getting that connection and feeling when you're doing the weight, not just doing it for the sake of it, like doing those reps and really thinking about that rep and just getting your body in those positions that you could do in the water on land. So when you go out there like a martial artist, you're you're ready to go. You've drilled it so many times it becomes second nature. Yeah. [00:24:01] Michael Frampton: No, strength training is so good. It's also for like strength training gives you it increases your body awareness actually, and just increases your maintains your bone density. And it's just it's so helpful. And if you're doing it do upper body. Lower body. It's it's about as doesn't get any more hard of a cardio workout than doing like a strength training circuit if you want to, you know, get the heart rate up. [00:24:26] Matt Grainger: What sort of work? What sort of stuff are you doing these days, like in your regime? [00:24:30] Michael Frampton:. Mine's so I had I've got,, I had ACL surgery in my early 20s and it's now almost, you know, bone on bone, basically. So a lot of my, a lot of my training is just keeping on top of that. so like, slow moving, heavy stuff with,, you know, have you seen the knees over toes guy? [00:24:55] Matt Grainger: Yeah, yeah. He's awesome. [00:24:56] Michael Frampton: Hey, backwards walking on the treadmill and just. Yeah, following some of his stuff. Uh, and just to keep the legs strong. Because it's interesting. Because they say it's bone on bone, right? And it can get like that, but your cartilage is gone. Your cartilage doesn't really come back. But there is scar tissue forms where the cartilage was. As long as that scar tissue is there, you're fine. If you do too much stuff and that scar tissue wears away. So if you do too much volume and you don't allow that scar tissue to to heal and reform and the fluids to come back, then it can be bone on bone, you get a real sore joint. But so now, as long as I keep the volume of what I'm doing on the knee, it's fine. You can actually you can actually go. [00:25:39] Matt Grainger: How many reps? [00:25:41] Michael Frampton: Actually, I would just sort of more like six reps. Only a couple of sets. But you know, because I've got a history of strength training. I know the form. I'm strong, I know what to do. But a backwards walking on the treadmill and some and lots of balance work as well, because it's actually those small little twitching movements in the joint that do the most damage. So if your balance is on point and your joint is nice and stable, then it's one of the big things as well. So keeping the balance, like standing on one leg with your eyes closed. Little things like that. Yeah I do. [00:26:16] Matt Grainger: I love the pendulum jumps with the, you know, the pendulum jump. So it's a one legged jump. Yeah. and we'll do that. More eyes closed as well. Yeah. When I coach a lot of the athletes as well, like before, they were competing, like, I'd say, like they'll do five jumps, eyes open, and then the last five closed. And it helps for that body awareness, you know, for late drops and. yeah, no big drops out of the lip and being aware of where their body is. Yeah. Yeah. And I even did it when I crack my head to check if I had concussion, I was like, yes, I'm fine. You know. Yeah. Yeah. I'm not a doctor. I'm not a doctor. But if you can jump one legged with your eyes closed, you pretty much. And you're fine. You don't have concussion. Yeah. Yeah. Yeah. [00:27:03] Michael Frampton: No, I do a bit of sprinting. Sprinting as well. Sprinting is really good for you. So I do a bit of that and I still do like the bodyweight gymnastics style strength training as well. Still doing that. Following a guy called, uh, Nardi. Oh, man, I can't even pronounce his name. Nardi Orejuela or I can't remember how to pronounce it, but it's functional performance training. He's doing a lot of really unique stuff. He's worth a follow. He's pretty out there with some of what he says, but he's also got some really interesting tips. A lot of, you know, not necessarily heavy weights, but functional, functional stuff. Just he's worth a follow. [00:27:39] Matt Grainger: Cool. yeah. [00:27:40] Michael Frampton: And just keeping on top of the diet, diet and sleep, man, that's like you mentioned, man. Just keeping a clean diet, getting enough sleep and giving a good balance of rest and stress. [00:27:49] Matt Grainger: Because, yeah, life can get stressful, but it's only what you make it really like. But yeah, if you if you sleep well, if you have a good sleep, you can conquer anything. Really. Hey, I'll find two. The shoulders are important. Like the rotator cuff muscles. Important to keep that on top of that. Just like maintenance work like prehab, like lightweights, like 10% of your body weight, just getting in all those different angles because you do you can, you know, when you're, you know, those days when you're paddling super hard trying to make that wave where it's hollow, you're going to put a lot of stress on the shoulder joint. And I've had seen so many mates like you look at you got to look at your mates who had surgeries, you know what I mean? Like, it's always so, shoulders, knees and hips if you look after those. And spine pretty much ahead of the game. Yeah. Yeah. [00:28:40] Michael Frampton: Hanging dude. Hanging for your shoulders. Really good. [00:28:45] Matt Grainger: Just hanging. Awesome. [00:28:46] Michael Frampton: Active and passive. Hanging. And, I mean, I'm lucky. When I was living in the US, I did. I did three different DNS courses., yeah. [00:28:55] Matt Grainger: Yeah, yeah, yeah, I remember you doing that. Yeah. [00:28:57] Michael Frampton: And so I do a lot of that sort of rehab style training still. And that's really good for shoulders and and core that helps keep my shoulders in check. [00:29:07] Matt Grainger: I remember, I remember you got injured and I did the Ido portal course. Yes, I remember you did. Yeah, I think you did your hamstring right. Yeah. That's right. Yeah. And I was a day before and he said, Matti, can you do this? And I went, yeah. And did a whole week with it. [00:29:22] Michael Frampton: Yeah. That's right. [00:29:23] Matt Grainger: Yeah. He was massive. It was massive on hanging. Yeah. And you know, the ring and the rings too. Yeah. And I find the rings or rings are better for a surfer too. Like doing chin ups, pull ups on a ring because you get that nice. Like you get that movement in the shoulder joint where it's just a straight bar. You don't really get that movement because we actually reach out and rotate our shoulder as we paddle. Yeah. So yeah. Yeah, yeah. You know, it was it was pretty. It was an interesting guy. Cool guy. Full on. Yeah. He is. Yeah. But yeah, I learned a lot. Yeah. [00:29:59] Michael Frampton: cool. Are you still doing ice baths? [00:30:01] Matt Grainger: Still doing that. [00:30:02] Michael Frampton: Yeah. [00:30:03] Matt Grainger: And our boss. And so on. Got an ice bath in the backyard and a sauna, which is lucky. And we got two at the gym now. We got two saunas and two ice baths. Wow. So. Yeah. Yeah. It's good. Everyone loves them. Yeah. Everyone's created a little community there. Yeah, yeah. It's awesome. [00:30:21] Michael Frampton: What about LA? Have you looked into Light Health? [00:30:24] Matt Grainger: I have seen it. I haven't really done it personally. And it just looks it looks pretty interesting. It's just a matter of time and money. Yeah. In our in our sauna. I do have some infrared, but, like, not, some lighting, but, you know, it's not huge. Have you been looking into it? Well, it's it's just really interesting. [00:30:42] Michael Frampton: There's this guy, Jack cruise, who's been on about it for years, but now that there's sort of like 20 years, but now there's all these scientific studies coming out proving his theories right about how important, sunlight exposure is for health and how it turns on certain genes like the Pomc gene and and how if you're exposing yourself to too much blue light after the sun's gone down, how that affects blood sugar and circadian rhythms. And but if I mean, if you're getting up and going, surfing every day and getting to bed on time, it's funny, that's all. [00:31:14] Matt Grainger: Like Huberman and all that, like, yeah, they say go out and play, you know, go get the sun. Yeah. And, I, we live on the East Coast here, so every early surf, you're like, looking into the sun exactly in the morning. You know, you're blinking, going oh. And, you know, different on the West Coast. Yeah. If you go to bed at the right time. And I try not to look at my phone before I go to bed. So, Yeah, I just try to banish that, put it away because. Yeah, that's a bad habit, isn't it? Just before looking at the screen, try to look at computers as well. So onto that in that way. Yeah. Yeah. You can just go. Yeah. Just basic stuff. Yeah. Keeping those circadian rhythms. Yeah. Haven't done the glasses or anything like that. Like the. [00:31:58] Michael Frampton: The blue blocking glasses. Yeah. [00:32:01] Matt Grainger: Dave Asprey and whatnot. [00:32:02] Michael Frampton: Yeah. Yeah, they get into it a lot. They go hardcore on everything. [00:32:06] Matt Grainger: They go hardcore. I'm like, no. How am I? It's none of them. Don't you think there's a fine line between how much time you got in the day and. [00:32:15] Michael Frampton: exactly. But I mean, David Beckham and his mates, they're spending a lot of money on, like, days. Dave Asprey has a goal to live to 120. I think he might have even said 100, 150. But like and be healthy and functional at that age. So he's making sure that, you know, every day he's doing as much as he can. So those guys are going. I don't know. [00:32:38] Matt Grainger: I don't know if I want to live that long. Yeah. It's damn sad. You know what I mean? Like, you kind of want to just die normally. You know, like. [00:32:45] Michael Frampton: With dignity. Yeah. [00:32:47] Matt Grainger: Dignity? Yeah. Like you don't have to go. Yeah. Yeah. [00:32:50] Michael Frampton: Because if you're the only, you're the only one doing it. And like, you're you're still alive and healthy. Yeah. Friends are dead. You're like. [00:32:58] Matt Grainger: What was that? I mean, let's talk about that all the time. Yeah. They just overboard and and almost bring a lot of anxiety, I think, to like trying to keep on point. Like you're not actually like they want to get to this goal of being this age, but they're not actually having fun in the present. Like it's like I've still got to live your life. Hey, you got to still have fun with your friends, with your friends. And, you know, like, I'm not like, a total. I'm. There's no way I'm a total monk. Like, I'm. I still eat really well, but if I, you know, if I'm with with friends and family, I'm not going to go. I'm not eating that because I'm this, you know, like, yeah, I'll still want to be part of the group, you know what I mean? Yeah, yeah. It's not going to kill me. Yeah. I don't want to have a good time with with my friends. I'm not going to be that guy that's like, oh, no, I don't do that. Because, I want to live to 150. [00:33:46] Michael Frampton: Exactly. Yeah. I'm going to go to bed at 8:00 on Christmas Day because you want to live to 150? [00:33:55] Matt Grainger: You know, it's kind of like. Yeah, it's counterintuitive. Really? [00:33:59] Michael Frampton: Yeah. [00:34:00] Matt Grainger: What about if you get to whatever, you get hit by a car? Exactly. You know. Exactly. I don't mean that in a bad way.. You got it. Still? Yeah. And it's funny, like, all this grounding, you know, we we hardly wear shoes in was, you know, you hardly wear shoes when I, when I hang out with you. Yeah, but hardly shoes. Oh, Maddy, you're wearing shoes today. That's weird. I'm like, oh, well, I had to go to remaining shoes. [00:34:27] Michael Frampton: I hate. [00:34:28] Matt Grainger: It. Yeah, yeah, yeah. [00:34:30] Michael Frampton: No, but that's the thing. All the stuff that's coming out in the latest health stuff, all these guys, it's what we do anyway. Especially as surfers. We get early morning sun. We're getting lots of grounding work because we're surfing in the ocean. That's the best way to get your. Your grounding done is in the ocean or walking on the sand in bare feet. We're getting it done anyway. But it's just interesting, all these studies coming out and and proving that. [00:34:55] Matt Grainger: You can you can buy a grounding mat and walk outside. Put your feet on the on the cold grass, you know, like, the cold sand. Like I'll be surfing the wave pool a lot lately and it's super fun. But you still don't get that, feeling of the energy or the ocean. Like, you know, it doesn't matter if your body surf, surf, body board, whatever. If you dive in the ocean for a swim, you always come out feeling amazing, don't you? Yeah. Just from it's from the negative ions though, isn't it. [00:35:24] Michael Frampton: Yeah. That's part of it. Yeah. [00:35:25] Matt Grainger: Yeah, yeah part of it. Yeah. And just maybe the salt, the energy of the waves just being in nature and. Yeah, it's funny, you can go on the wave pool and you have a good time. You don't get that buzz of that feeling on your whole body from the natural waves. Yeah. And the salt and all that. Yeah. [00:35:46] Michael Frampton: How much time have you spent in the wave pools? [00:35:49] Matt Grainger:there's a new one in Sydney now. Sydney and I. Every Thursday I teach a fitness class to the staff. I've been doing that for the past six weeks. So I go out every Thursday and I make sure I serve from 4 to 5, and then I run the class at 530 to 630. So that's pretty cool. Like, I'll ride my little five three Bobby quad and, get about 20 waves. And then we ran our we ran a pretty cool course the other week. We did a get ready for your master class. It was like an endo masterclass clinic. So we taught people how to ride left tubes. So we had the expert mode, which is just a barrel. It's pretty cool. You take off, you can do a Rio or just a set up turn and get this nice tube. That's a pretty cool tube. Like the barrel is wider than it is high. Yeah, you got to get quite low in the tube. And then it kind of turned the corner a bit like macaronis. So we did um, we did about 30 minutes. I broke down all the best surfers in the world getting tubed on the TV screen have had eight participants, and so we broke that down for placement, for backhand front side, you know, getting and then we did movement patterns like mobility patterns to open up people's hips and, and ankles, because that's pretty much what you need when getting low in tubes and most tube riding. [00:37:08] Matt Grainger: So we did that, we went and surfed for an hour. Everyone got about 12 waves. And then we there's a I it's crazy. They film this. I called Flow State on the left and the right, but we're only on the left. You come in and it's got all the clips of you. So I got a coaches password. So I went through everyone's clips and broke down what they were doing. Right. What they're doing wrong. Yeah, it was rad. And then we had had lunch and then we did apnea training. So then we went into the leisure pool, which is heated because the wave pool is only about 11 degrees at the moment. So yeah, it's quite it's quite cold. Yeah. So they just pulled 28. So we, we taught them the science of breath holding. Then we went and did it in the water. And then she did a chat on our endo. What's it like in your first aid kit? And, you know, rough cuts? Yeah, it was awesome. That was a that was a full day. It was fun. [00:38:00] Michael Frampton: All right. So I did. [00:38:01] Matt Grainger: That., had some fun days with the Surface Gym crew. We'll book out the pool for two hours. And so two different modes, one the tube, the expert modes and tube. And they've got advanced, which is half turns, half tube. Yeah. It's pretty cool. Good fun. And then Isabella Nichols two. She'll fly down and we'll I'll coach her for two days before an event. So before Huntington, we tested out two of the boards. See what you actually got. Two brand new boards of the HD and then obviously had more, but she had these two boards that she thought were going to be the ones. And they were so pretty cool to work that out. Yeah, we did some also some work before Bolido. So it's not a it's a good coaching tool. Yeah., because you got you guaranteed getting one left and right, so I'll book it. We'll book a session on the right and the left, and you're right there that she can come in and break it down each wave and go through some foot placement and hand placement stuff where you place the board on the wave and back out there. Yeah. So it's pretty cool. And you got all the footage on film as well and also got the flow state. [00:39:04] Michael Frampton: All right. It's like the driving range for surfers. [00:39:07] Matt Grainger: Yeah it is. It's the full driving range. So it keeps you fit too. Like it's actually it's a full leg workout because the way you get weaker, you've got to stay right in the pocket and push real hard with your feet and your hips. Yeah a lot of. Yeah. It's pretty interesting. Yeah. It's good. Good fun. You feel like especially in the tube major. Every time I'm just on the tube I feel like a 15 year old kid again. Like you're guaranteed a barrel. You know, you're guaranteed 15 to 20 barrels that up and. Yeah. Pretty amazing. [00:39:34] Michael Frampton: Oh, that's so good. you're still doing good. Did you. Are you still taking people to macarons as well? [00:39:40] Matt Grainger: Yeah, we've got one coming up, yeah. Next February, March 2025. We're doing. Chaz is doing the movement, and I'm doing the surfing right. Yeah, we've got two and I got a goose and Ari, who helped us as well as coaching. They're awesome guys and good coaches. Yeah. Yeah. It's rad. Yeah. So we basically surf from 6 a.m. till 1130 and there's two filmers there. So they the filmers get all the footage and then we, we break down the footage at 1:00 for about an hour, and then we'll go surfing again. And then sometimes if the waves are small, we'll do apnea training in the pool. So that's like a week, seven day classes or seven day clinics. So and then some people do two weeks. Yeah. Wow. But yeah it's super fun. And you know, we go to the Thunders as well because, uh, McKenzie's small. It's always two foot bigger up there. So yeah, it's good fun. Yeah. It's an awesome, awesome clinic because it's such a mechanical wave that goes from 1ft to 6 foot. Such a rippable wave. You know, just in the pocket. You can work on people's techniques and you see people improve real quick because they've got a running wall. It's not like a, you know, sitting right here, but sometimes you can just get close down. If it's the south swell you just got, you know, the people can only do one turn if that. Obviously if it's perfect, no swells here. Great. You know, all the all the, all the beaches are lining up. Machias is unbelievable. You can do four turns so you can really work on people's, you know how they you know how they sort of start the wave speed generation where they do their bottom turn, their top turn and good place for an upper body rotation. Yeah. It's cool. Yeah. It's good fun. Yeah. All right. That's it. [00:41:29] Michael Frampton: They all filled up. Clean up? [00:41:31] Matt Grainger: Uh. Not yet. No, I think there's still some spots left. Yeah. So they're filling macaroni, doing the marketing right now for next year, but yeah, they get. Yeah. We got some good numbers this year. I think next year is going to be even better. Yeah. So it's a good gig? Yeah. It's good fun. Yeah. And, you know, good, good bonding with people. Everyone's there to learn and have a good time. [00:41:51] Michael Frampton: I'll put a link to to details about that. Show notes. [00:41:55] Matt Grainger: Awesome. Yeah. Awesome. [00:41:57] Michael Frampton: You guys had a big swell there a few days. Yeah. We had. [00:42:01] Matt Grainger: Yeah. Last week. Uh, last. Yeah, we had a massive swell. Monday. Tuesday. Wednesday. Thursday. Friday. Only bummer had really strong southerly winds. So we, being the captain, towed the car and naughty bomb in the mornings when it was southwest. And then the wind just came up and blew it out. The dead man's was on. Yeah. We got to surf that on our own. Dead man's pumping. Have a look at that. [00:42:27] Michael Frampton: I saw the footage. Yeah, some of it, but it was. [00:42:30] Matt Grainger: It wasn't many people making them. Hey, it looked pretty gnarly. How cool is it? If you have a look at, uh, this is living by Carl how often he flew. He flew all the way over for it. [00:42:41] Matt Grainger: He does that. does that blog and, Yeah, he did. He didn't even make a way. Like a proper big one. He didn't make one way. He broke in the board, got smashed. He was coming this way. Gnarly. Cuz it's kind of like the heavy cake. Then it's got a step. Yeah. And if it doesn't open up, it just collapses on you. Yeah. And you don't know when you're paddling in. You're going to be a good one or not. there's one guy called Sam Jones. Got a cracker like he made. He actually made a really good one. But the rest of the crew. Yeah. Pretty much got smashed. There was a lot of carnage. Choo choo. Kelleher did a big airdrop. Dislocated his elbow joint., he got that? no. He just airdropped and then went back over the fall. Popping the elbow. Yeah, I'm kind of done with that wave. I know it's pretty gnarly backside. You just be looking for an injury and it's crowded now. Like I have to surf it on my own with, like, you know, 4 or 5 people. And now it's everyone's out there trying to get their photo taken or their clip, which is cool. You know, they're all younger and there'll be 30, 40 people out on a semi-closed reef that's 10 to 12 foot. [00:43:52] Matt Grainger: So we can get the jet skiing off the off the car and step on it. Right? Yeah. Yeah. And then we can check out Makaha, you know, go. Makaha. German banks, North Bay cruise around being the captain. It's fun. Yeah. Yeah. You got to be ready to go for dead man's like I've. I've snapped boards out there. I've had 30 sea urchins at my 40 out there once. I just went over the falls and landed feet first. And that was pretty gnarly. Injury. Went to hospital. Like, I, I couldn't walk, so I had to paddle back to North Steyne, back to the school, and drove up to the hospital. And they couldn't even get they left about four in there. And then three stayed. Three stayed in there for about three months. And and I Right when I popped out about that big, like three months later when I went snowboarding. gnarly. I remember Barton Barton Lynch actually got. He had to go to surgery with sea urchins out there. Scotty Romaine broke his back about four years ago. Out there, captains broke ins, MCL, PCL. Just copy breaking your ribs. Yeah, that's a good way to get injured. But it's if you're young, young buck and you want to charge, go for it. [00:45:03] Michael Frampton: Well you gotta you gotta pay to play sometimes. [00:45:06] Matt Grainger: Yeah. Yeah yeah. The, the the risk out there that have outweigh the rewards. But yeah there's some really there's some good surfing going on. Some of the young guys the young guys in pressure like so grueling. Lex O'Connor, some of the young dudes are like 18 year olds just charging it and making barrels, too. So. But this last world was pretty wonky. But we had a real good swell a week before that. Like a beast or a swell like Narromine was off its face, mouth narrower. We had like nor'west winds and eight foot barrels and that was that was pretty fun. So yeah, that was a more user friendly. And it was pumping north out or the whole East Coast. Yeah. On the Sydney Northern Beaches was going off. So yeah that went that went for three days. So we've had a really good year. Last year was about like a pretty bad winter. Yeah. To be here for Sydney and the sandbanks are good because we had that big swell. But yeah, pretty pretty stoked. What about yourself? Any waves your way? [00:46:05] Michael Frampton: Some. Not. Not too many. We've had a shit winter, actually. We've had heaps of. Usually you get the southerly swells here where I'm staying at the moment, but,, I've just been heaps of northerly nor east swells of low period for some reason. Almost like summer had weird weather patterns here. The south swells that come through have heaps of west in them, so they just go straight past. I don't know. [00:46:27] Matt Grainger: And the baits are good. [00:46:28] Michael Frampton: There's there's points and river bars around here. So we just need a decent high, long period swell and it turns on, but it still goes surfing but. And get waves and had a great summer. Great summer with the kids. Yeah. [00:46:42] Matt Grainger: Awesome. [00:46:43] Michael Frampton: But the winters. Yeah. Average winter here. And it's pretty. [00:46:47] Matt Grainger: Crazy. We've actually got,, the water's cold, like, it's, 14 degrees. Yeah. So sometimes it'll be. It'll be 20 in winter usually. But this year it's cold. Yeah, but the good. Yeah. So every morning pretty much offshore. So that's kind of cool. Yeah. With this with this cold water being lucky. Yeah. Random. [00:47:06] Michael Frampton: The water here, the water here is warmer than usual. I can still go surfing in A23 at the moment. No way. Yeah. The water's so warm here. It's just all these east and northeast flow. It's keeping the water warm. [00:47:19] Matt Grainger: That's pretty cool. Yeah, we. The wave pools. The wave pool. Actually, the concrete holds the cold. yeah, I bet I pulled about about 1111. [00:47:29] Michael Frampton: That's 43 bodies business. [00:47:31] Matt Grainger: Yeah, yeah, I just I don't wear booties, but I the guy's wearing gloves and hoods and just make sure you paddle out real quick and keep yourself warm. But yeah, last year we were last year we went to, Mexico and I. Yeah. So that was cool., but this year I'm just going to hang back. I've been building this app called The Surfer's Compass, so I want to get that out by the 1st of September. Hopefully I'll be doing that for a year. So just breaking down all the best surfers in the world. Women and men take offs, paddling, bottom turn, top turns, cuttings, airs, tubes and then throwing in movement patterns that will help those maneuvers and then breathwork and mindset. Yeah. So that's been a fun little project. [00:48:15] Michael Frampton: All right. [00:48:16] Matt Grainger: So yeah be working on that. I was helping with the graphics and Joe Barker with all the edits. But yeah, that's keeping me busy. It's like a, you know like you've done a lot of projects and you just want to get it done? Yeah. I mean, I'd want to do it right, but we were told we probably could have had it done in May, but I want to do it perfect. So yeah, hopefully we get it out by. Yeah. So I got like Ethan Ewing, Mick Fanning and Kelly Slater, Jeff Gilmore, Aaron Brooks, Isabella Nichols. [00:48:42] Michael Frampton: Parker cool. Look forward to seeing it. [00:48:44] Matt Grainger: Yeah. So that's what's keeping me busy. Yeah, yeah. And all the other stuff. The surf school and and the surf gym. [00:48:51] Michael Frampton: And all the barrels. [00:48:53] Matt Grainger: All the barrels. [00:48:54] Michael Frampton: Oh, sweet. You have to let let us, let us know when it's when it's released. And I'll spread the word. [00:48:58] Matt Grainger: Sure. That'll be awesome. Yeah. But yeah, you can't beat a barrel, can you? I always say to people, once you get it, why don't you get tubed? You're done. You won't be able to hold a relationship or a job and. [00:49:09] Michael Frampton: Yeah, it's addictive. Yeah. Healthy addiction though. It's on my list. I'll probably sit down with the boys this evening and we'll watch the replays and stuff. Yeah, one. [00:49:18] Matt Grainger: Of the local boys did really well, so yeah, it's pretty, pretty good result. You got to check it out. Yeah, it's actually awesome spectacle. How was,. Did you see the the big day? Yeah. [00:49:29] Michael Frampton: Yeah. No, I watched that with. [00:49:31] Matt Grainger: Joe and Ramsey. Booker. Joe, do you reckon they were charging harder than the WSL because there was more on the line, like, you know, medals and, like, they always charge in the WAFL that they go hard as. But some of them are not the nailing. Some of the Wipeouts were heavy weren't they. But yeah. [00:49:47] Michael Frampton: And also. [00:49:48] Matt Grainger: Connor O'Leary. [00:49:49] Michael Frampton: Though also like they had different camera angles too to the. So I don't know if they had even more expensive cameras to it just. Yeah different like just a higher level production as well. I think that helped. but certainly in the Medina it was just always everything Medina does just looks effortless, doesn't it? [00:50:06] Matt Grainger: It's that good, isn't it? Yeah. Yeah. He's amazing. Yeah. He's. He's,. Yeah. There. Ethan Ewing. Yeah. They're solid as those guys. But it was good seeing the other guy from Peru. Yeah, it was Cabrera, wasn't it? Yeah. Like,. Yeah. Just seeing the other countries. That's pretty good, isn't it, about the Olympics, like, cared a lot more diversity. Yeah. I mean, I love the WAFL, but especially when they do the cup after the cup is just too much familiar., everyone's too familiar. You know, you go,, I've seen this heat before, even though it's in a different location. But it's good when you get wild cards and that variety and you just think,, I've seen another angle of surfing, you know, like, wow, this guy's insane. [00:50:48] Michael Frampton: All right. Matt. Hey, it's just gone 3:00. I better go in there. I got to do school pickup now, but thanks for thanks for doing the show again. Really appreciate it. [00:50:57] Matt Grainger: Awesome, mate. Awesome, brother. Take it easy. [00:51:00] Michael Frampton: Good to catch up. [00:51:01] Matt Grainger: Good one. Hopefully. See you when you come to Sydney. [00:51:03] Michael Frampton: That'd be great. Yeah. For sure. We'll be over there at some point., yeah. Keep me in. Keep me in the loop. Yeah, yeah. Keep me in the loop with the app. So. Yeah. Excellent. [00:51:13] Matt Grainger: That'd be cool. Awesome. Awesome, mate. [00:51:15] Michael Frampton: Thank you for tuning in to the Surf Mastery podcast. If you enjoyed this episode, please share it with a friend. Also, the best way that you can help support and grow the show is to subscribe, rate and review on whatever app you're using, be it Spotify, Apple Podcasts, and of course, we are now on YouTube, so you can watch the video version of this podcast on YouTube. Be sure to check that out. Also, go to Surf mastery.com for more surfing tips via the blog. You can also book in a personal online surf coaching session with me, also at Surf mastery.com. There are two free downloadable PDFs, one with the five best tips from this show, and one the five best exercises to improve your surfing. So go to Surf mastery.com on the home page there. You'll see them. Until next time, keep surfing. Matt Grainger on the Surf Mastery Podcast
In the episode, we will explore a common problem with Autism- the Gastrointestinal Tract. The one consistent finding with Autism and GI is a problem exists. However, research on complicated in these complicated and complex areas of human biology despite what appears to be tight controls in the studies. However, one crucial component is missing- Light. In this episode, we will cover how biology structures order from the light input and the chaos from the environment.Major Areas include Enterochromaffin Cells, Serotonin, Aromatic Amino Acids, Vitamin D, Enteric Nervous System, the endocrine systems, and the Hypothalamic-Pitutary-Adrenal Axis.Cause of Autism: https://podcasts.apple.com/us/podcast/from-the-spectrum-finding-superpowers-with-autism/id1737499562?i=1000662271496Su study: https://www.nature.com/articles/s41564-024-01739-1Sunlight and Vitamin D: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3897598/Multi-Axis-Meta-Analysis https://www.nature.com/articles/s41598-022-21327-9Quantum Engineering 33, 54, and 55 https://www.patreon.com/DrJackKruse/posts(0:00) Autism and the GI Tract; inconsistent research; Order versus Chaos- Light and Environment and Health Conditions(3:10) The GI Tract; Gut-Brain Axis; Gut Microbiome and Various Nervous Systems(6:22) POMC; HPA; Stress example(8:19) Common Autism problems in the GI(9:23) Enterochromaffin Cells; Serotonin; Immune and Inflammation(14:09) Melanin/POMC; Clock-Timing; Omentum(16:31) Real-life Acute GI Fix; Bacteria makes Dopamine in the Gut(19:04) Vitamin D Receptors and more Clock-Timing(22:13) Obesity and Autism connection? (uncoupled systems); Biosynthesis of Vit D and specific Wavelength of Light with Shared Biological Processes- DNA, RNA, Aromatic Amino Acids(24:33) Avoiding UV Light implications(26:18) Scientific Literature; Archaea, Bacteria, Fungi, Virus; "confounding" data(30:03) Ubiquinol-7, COQ10, Thiamine Diphosphate; TCA cycles(32:38) Controls (plural) in Research and lack of Control (singular); LIGHT is GREATER than FOOD(38:27) Reviews/Ratings and Contact InfoX: https://x.com/rps47586Facebook: https://www.facebook.com/fromthespectrum.podcastEmail: info.fromthespectrum@gmail.com
Welcome back to the Evolving Wellness Podcast! In this episode, we're diving deep into the intersection of circadian and quantum biology with our special guest, Dr. Alexis J Cowan. Join us as Dr. Cowan shares her incredible journey from battling chronic health issues to discovering the transformative potential of sunlight in healing. From decoding the mysteries of gut microbiomes to unlocking the therapeutic benefits of UV light, this episode offers practical strategies to optimize your metabolic health. Explore beyond the confines of traditional science and embark on a holistic journey toward well-being. Tune in for illuminating discussions, actionable insights, and a roadmap to holistic living. Check Out Dr. Alexis J Cowan Instagram LinkedIn Courses Podcast Youtube Website The key moments in this episode are: 2:34 - Dr. Cowan's personal health story 6:55 - The gut microbiome 8:25 - Mold's effect on your mitochondria 13:53 - Mitochondrial function & UV light 16:35 - Dr. Cowan's PHD research 20:37 - UV light and the microbiome 22:17 - Changing how we study the sun 27:46 - The melanocortin pathway & POMC effects on appetite 30:17 - Healing mold exposure with circadian & quantum biology 35:28 - Healing with the sun 39:03 - Healing in extreme climates 42:42 - Deuterium depletion 44:50 - Working out outdoors vs indoors 48:14 - The shortcomings of the current scientific framework 53:07 - The fallibility of blood labs 55:48 - Our body's water network 58:40 - Cytochrome 4, ATP, and our mitochondria 1:00:56 - Cellular hydration 1:02:15 - Astro Herbalism 1:05:07 - Contacting Dr. Cowan This video is not medical advice & as a supporter to you and your health journey - I encourage you to monitor your labs and work with a professional! ________________________________________ Click here to get all my free guides and product recommendations to get started on your journey! Check out all my courses to understand how to improve your mitochondrial health & experience long lasting health! (Use code PODCAST to save 10%) Sign up for my newsletter to get special offers in the future!
Note: This podcast is a companion to the Ground Truths newsletter “A Big Week for GLP-1 Drugs”Eric Topol (00:06):It is Eric Topol with Ground Truths, and with me today is Dr. Daniel Drucker from the University of Toronto, who is one of the leading endocrinologists in the world, and he along with Joel Habener and Jens Juul Holst from the University of Copenhagen and Denmark, have been credited with numerous prizes of their discovery work of glucagon-like peptide-1 (GLP-1) as we get to know these family of drugs and he's a true pioneer. He's been working on this for decades. So welcome, Daniel.Daniel Drucker (00:43):Thank you.Eric Topol (00:45):Yeah, it's great to have you and to get the perspective, one of the true pioneers in this field, because to say it's blossom would be an understatement, don't you think?Daniel Drucker (00:57):Yeah, it's been a bit of a hectic three years. We had a good quiet 30 plus years of solid science and then it's just exploded over the last few years.Eric Topol (01:06):Yeah, back in 30 years ago, did you have any sense that this was coming?Daniel Drucker (01:14):Not what we're experiencing today, I think there was a vision for the diabetes story. The first experiments were demonstrating insulin secretion and patents were followed around the use for the treatment of GLP-1 for diabetes. The food intake story was much more gradual and the weight loss story was quite slow. And in fact, as you know, we've had a GLP-1 drug approved for people with obesity since 2014, so it's 10 years since liraglutide was approved, but it didn't really catch the public's attention. The weight loss was good, but it wasn't as spectacular as what we're seeing today. So this really has taken off just over the last three, four years.Eric Topol (01:58):Yeah, no, it's actually, I've never seen a drug class like this in my life, Daniel. I mean, I've obviously witnessed the statins, but this one in terms of pleiotropy of having diverse effects, and I want to get to the brain here in just a minute because that seems to be quite a big factor. But one thing just before we get too deep into this, I think you have been great to recognize one of your colleagues who you work with at Harvard, Svetlana Mojsov. And the question I guess is over the years, as you said, there was a real kind of incremental path and I guess was in 1996 when you said, well, this drug likely will inhibit food intake, but then there were gaps of many years since then, as you mentioned about getting into the obesity side. Was that because there wasn't much weight loss in the people with diabetes or was it related to the dose of the drugs that were being tested?Why Did It Take So Long to Get to Obesity?Daniel Drucker (03:11):Well, really both. So the initial doses we tested for type 2 diabetes did not produce a lot of weight loss, maybe 2-3%. And then when we got semaglutide for type 2 diabetes, maybe we were getting 4-5% mean weight loss. And so that was really good and that was much better than we achieved before with any glucose lowering drug. But a lot of credit goes to Novo Nordisk because they looked at the dose for liraglutide and diabetes, which was 1.8 milligrams once daily for people with type 2 diabetes. And they asked a simple question, what if we increase the dose for weight loss? And the answer was, we get better weight loss with 3 milligrams once a day. So they learn that. And when they introduced semaglutide for type 2 diabetes, the doses were 0.5 and 1 milligrams. But in the back of their minds was the same question, what if we increased the dose and they landed on 2.4 milligrams once a week. And that's when we really started to see that the unexpected spectacular weight loss that we're now quite familiar with.Eric Topol (04:16):Was there also something too that diabetics don't lose as much weight if you were to have match dose?Daniel Drucker (04:22):Yeah, that's a general phenomenon. If one goes from either diet to bariatric surgery, and certainly with weight loss medicines, we tend to see maybe two thirds to three quarters of the amount of weight loss in people with type 2 diabetes. We don't really understand it. The brain pathways are probably resistant to some of the pathways that are activated that lead to weight loss, and it's really an interesting observation that needs further study.The Brain EffectEric Topol (04:50):Yeah, it's fascinating really. And it might've at least in part, held up this progress that has been truly remarkable. Now, recently you published a paper among many, you're a very prolific scientist, of course, physician scientist, but back in December in Cell Metabolism was a very important paper that explored the brain gut axis, the ability to inhibit inflammation and the mechanism through Toll-like receptors that you were seeing that. So maybe you could summarize the fact that you saw this, you were quoted in this Atlantic piece by Sarah Zhang, the science behind Ozempic was wrong. The weight loss effects of GLP-1 drugs have little to do with the gut and basically claiming that it's related to the effects on the brain, which of course could be reduced inflammation, reduced or inhibiting centers of addiction craving, that sort of thing. So how do you interpret your recent results and ongoing studies regarding GLP-1's effect on the brain?Daniel Drucker (06:02):Sure, so to be clear, I don't think that was a quote. I never would've said the science behind Ozempic was wrong. I think that was a headline writer doing what they do best, which is catching people's attention. I think what I was trying to say is that where this field started with insulin secretion first and then weight loss second, those are clearly very important pharmacological attributes of GLP-1. But physiologically, if we take GLP-1 away or we take the receptor away, you don't really develop diabetes without GLP-1. You don't really gain a lot of weight without GLP-1. So physiologically it's not that important. Why do we have GLP-1 in the distal gut? I think physiologically it's there to defend against infection and reduce gut inflammation. But we noticed that GLP-1 reduces inflammation in many different places in the heart and blood vessels and in the liver and many organs where you don't see a lot of GLP-1 receptors and you don't see a lot of GLP-1 receptors on immune cells.Daniel Drucker (07:04):So that really led us to the question, well, how does it work and affect all these organs where we don't see a lot of the receptors? And that's where we landed on the brain. Obviously the nervous system can communicate with many different cell types in almost every organ. And we identified neurons that expressed the GLP-1 receptor, which when blocked abrogated or completely eliminated the ability of GLP-1 to reduce inflammation in the periphery in white cells or in lungs. So it's been known for some time that the brain can control the immune system. So this is just the latest piece in the puzzle of how GLP-1 might reduce inflammation.Eric Topol (07:49):And just to be clear, I was quoting the Atlantic headline, not you that you were quoted within that article, but this is something that's really interesting because obviously GLP-1 is made in the brain in certain parts of the brain, it's transient in terms of its half-life made from the gut. But when we give these drugs, these agonists, how does it get in the brain? Because isn't there a problem with the blood brain barrier?Daniel Drucker (08:22):So I don't think the drugs get into the brain very well. We have a lot of data on this, so people have done the classic experiments, they either make radioactive ligands or fluorescent ligands, and they look how much gets in it and not very much gets in beyond the blood-brain barrier. And we also have big drugs that are immunoglobulin based and they work really well, so they don't get into the brain very much at all. And so, the way I describe this is that GLP-1 talks to the brain, but it doesn't directly get into the brain to meaningful extent, it does communicate somewhat there are areas obviously that are accessible in the area of the stream and circumventricular organs, but most of the time we have this communication that's not well understood that results in the magic that we see. And there are some discussions around for the neurodegenerative disease story where GLP-1 is being looked at in Parkinson's disease and in people with Alzheimer's disease. Would you be able to get more benefit if you could get the drugs into the brain to a greater extent, or would you simply increase the adverse event profile and the adverse response? So really important area for study as we begin to go beyond diabetes and obesity.Eric Topol (09:41):Yeah, I mean as you're pointing out, there's two ongoing trials, pretty large trials in Alzheimer's, early Alzheimer's, which may be a little bit too late, but at any rate, testing GLP-1 to see whether or not it could help prevent progression of the disease. And as you also mentioned, diseases and Parkinson's. But I guess, so the magic as you referred to it, the gut -brain axis so that when you give the GLP-1 family of drugs, we'll talk more about the double and triple receptor in a moment, but when you give these drugs, how does the message you get from the gut to the brain would you say?Daniel Drucker (10:27):So pharmacologically, we can give someone or an animal the drug, it does reach some of the accessible neurons that have GLP-1 receptors, and they probably transmit signals deeper into the brain and then activate signal transduction. So one way to look at it, if you use c-fos, the protein, which is an immediate early gene, which is increased when we activate neurons, we see rapid activation of c-fos in many regions that are deep within the brain within minutes. And we know that GLP-1 is not getting directly to those neurons, but it's activating pathways that turn on those neurons. And so, there's probably a very intricate set of pathways that sense the GLP-1 and the accessible neurons and then transmit those signals deeper into the brain.Double and Triple Receptor AgonistsEric Topol (11:18):Okay, well that makes sense. Now, as this has been moving along in obesity from semaglutide to tirzepatide and beyond, we're seeing even more potency it appears, and we have now double and triple receptors adding into glucagon itself and the gastric inhibitory polypeptide, and there's mixed data. So for example, the Amgen drug has the opposite effect on GIP as does the dual receptor, but comes out with the same weight loss I guess. How do we understand, I mean you know these gut hormones inside and out, how do we get such disparate results when you're either blocking or revving up a peptide effect?Daniel Drucker (12:13):Yeah, it's a mystery. I always sort of joke that you've invited the wrong person because I don't fully understand how to reconcile this honestly. There are some theories you could say that tirzepatide may possibly desensitize the GIP receptor, and that would align with what the GIP receptor blocking component is. And so, I think we need a lot of research, we may actually never know in humans how to reconcile these observations. I think we can do the experiments in animals, we're doing them, other people are doing them to look at the gain and loss of function and use best genetics. But in humans, you'd have to block or activate these receptors in very specific populations for a long period of time with tools that we probably don't have. So we may not reconstruct. We may end up with Maritide from Amgen that's producing 15-20% plus weight loss and tirzepatide from Lilly, that's spectacular, that's producing more than 20% weight loss. And yet as you mentioned at the GIP level, they have opposite effect. So I don't think we fully understand. Maybe your next guest will explain it to you and invite me on. I'd be happy to listen.Eric Topol (13:27):Well, I don't know. I don't think anybody can explain it. You've done it as well as I think as possible right now. But then we have the triple receptor, which it seems like if you take that drug, you could just go kind of skeletal. It seems like there's no plateau and its effect, that is I guess is it retatrutide, is that the name of it?Daniel Drucker (13:47):Retatrutide, yeah.Eric Topol (13:48):Retatrutide, okay. And then of course we're going on with potentially oral drugs or drugs that last for a year. And where do you see all that headed?Daniel Drucker (14:00):So I think the way I describe innovation in this field is there are two buckets that we've talked about today. So one bucket is the new molecule, so we're going to have all kinds of different combinations that will be peptides, that will be small molecule orals, the NIH is funding innovative programs to see if we can develop cell-based factories that produce GLP-1. There are gene editing and gene therapy approaches. So there are going to be multiple different molecular approaches to delivering molecules that are better and hopefully easier to take maybe once monthly, maybe every six months. So that's really exciting. And the other obvious bucket is the disease that we're targeting, so we started off with type 2 diabetes. We're now firmly established in the obesity field. In your field, we've seen consistently positive cardiovascular outcome trials. We had a press release a few months ago in October - November saying that semaglutide reduces chronic kidney disease. We have trials underway with peripheral artery disease with Parkinson's disease, with Alzheimer's and a number of neuropsychiatric conditions. So I think we're going to see both innovation on the molecule side as well as expanding if the trials are positive, expanding clinical indication. So it's going to be a pretty exciting next couple of years.Eric Topol (15:21):Right, no question. And as you well know, just in the past week, the FDA gave the green light for using these drugs for heart failure with preserved ejection fraction, which was an important randomized trial that showed that. Now there's got to be some downsides of course there's no drug that's perfect. And I wanted to get your comments about muscle loss, potentially bone density reduction. What are the downsides that we should be thinking about with these drugs?Side EffectsDaniel Drucker (15:54):Sure, so the known side effects are predominantly gastrointestinal. So we have nausea, diarrhea, constipation and vomiting. And very importantly, if those side effects are severe enough that someone can't eat and drink for 24 hours, we need to tell them you have to seek medical attention because some people will get dehydrated and rarely get acute kidney injury. This is rare, but it's described in many of the outcome trials, and we definitely want to avoid that. Gallbladder events are probably one in several hundred to one in a thousand, and that can be anywhere from gallbladder inflammation to gallbladder stones to biliary obstruction. Don't fully understand that although GLP-1 does reduce gallbladder motility, so that may contribute. And then very rarely we're seeing reports of small bowel obstruction in some people difficult to sort out. We don't really see that in the large clinical trials, but we have to take people at there were, we haven't seen an imbalance in pancreatitis, we haven't seen an imbalance of cancer.Daniel Drucker (17:01):There is no evidence for clinically significant bone disease either at the level of reduced bone densities or more importantly at the level of fractures. And we have a lot of real world data that's looked at that. Now muscle losses is really interesting. So when the initial drugs were approved, they didn't produce much weight loss. We didn't think about it. Now that we're getting the 15 20% plus, the question is, will we see clinically significant sarcopenia? And I use the word clinically significant carefully. So we definitely see muscle lean mass loss on a DEXA scan, for example. But what we're not seeing so far are people who are saying, you know what my grip strength is weak. I can't get up off the chair. I have trouble reaching up into the cupboard. My exercise or walking capacity is limited. We're not seeing that. In fact, we're seeing the opposite.Daniel Drucker (17:53):As you might expect, people are losing weight, they're less achy, they can move more, they can exercise more. So the question is buried within that data, are there some individuals with real clinical sarcopenia? And as we get to 25% weight loss, it's very reasonable to expect that maybe we will see some individuals with clinical sarcopenia. So you're very familiar. There are half a dozen companies developing medicines to promote fat mass loss and spare muscle with or without semaglutide or tirzepatide. And this is a really interesting area to follow, and I don't know how it's going to turn out. We really have to see if we are going to see enough clinically significant muscle loss and sarcopenia to merit a new drug category emerge, so fascinating to follow us.Eric Topol (18:46):No, I'm so glad you reviewed that because the muscle loss, it could be heterogeneous and there could be some people that really have some substantial sarcopenia. We'll learn more about that. Now that gets me to what do we do with lifelong therapy here, Daniel, where are we going? Because it seems as though when you stop these drugs, much of the benefit can be not potentially all, but a substantial amount could be lost over time. Is this something that you would view as an insulin and other hormonal treatments or how do you see it?The Question of ReboundDaniel Drucker (19:26):Yeah, so it's fascinating. I think that traditional view is the one that you just espoused. That is you stop the drug, you regain the weight, and people are concerned about the rebound weight and maybe gaining more fat and having less favorable body composition. But if you look at the data, and it's coming very fast and furious. A few months ago, we saw data for a tirzepatide trial, one of the surmount obesity trials, the first author was Louis Aronne in New York and they gave people tirzepatide or placebo for 38 weeks. And then they either continue the tirzepatide or stop the tirzepatide. One year later, so no tirzepatide for one year, more than 40% of the people still managed to keep at least 10% of their weight off, which is more than enough in many people to bestow considerable metabolic health. So I think there are going to be people that don't need to take the medicines all the time for weight loss, but we must remember that when we're excited about heart attacks and strokes and chronic kidney disease, there's no evidence that you can stop the medicines and still get the benefits to reduce those chronic complications.Daniel Drucker (20:46):So we're going to have to get much more sophisticated in terms of a personalized and precision medicine approach and ask what are the goals? And if the goals are to reduce heart attack strokes and death, you probably need to stay on the medicine if the goals are to achieve weight loss so that you can be metabolically healthy, there may be a lot of people who can come off the medicine for considerable amounts of time. So we're just learning about this. It's very new and it's really exciting.Suppressing Inflammation as the Common ThreadEric Topol (21:11):Yeah, no question. And just going back to the inflammation story in heart disease, it was notable that there were biomarkers of reduced inflammation in the intervention trial before there was any evidence of weight loss. So the anti-inflammatory effects here seem to be quite important, especially with various end organ benefits. Would you say that's true?Daniel Drucker (21:35):Yeah, I think that's one of my favorite sort of unifying theories. If we step back for a minute and we come into this and we say, well, here's a drug that improves heart disease and improves liver inflammation and reduces chronic kidney disease and may have some effect on atherosclerosis and is being studied with promising results and neurodegenerative disease, how do we unify all that? And one way is to say all of these chronic disorders are characterized by a component of chronic inflammation. And Eric, it's fascinating. I get reports from random strangers, people who've been on tirzepatide or people who have been on semaglutide, and they tell me, and you'll be fascinated with this, they tell me, my post Covid brain fog is better since I started the drug. They send me pictures of their hands. These are people with chronic arthritis. And they say, my hands have never looked better since I started the drug. And they tell me they've had ulcerative colitis for years on biologics and all of a sudden it's in remission on these drugs. So these are case reports, they're anecdotes, but they're fascinating and quite consistent with the fact that some people may be experiencing an anti-inflammatory effect of these medicines.Eric Topol (22:55):And I think it's notable that this is a much more potent anti-inflammatory effect than we saw from statins. I mean, as you know, well they have an effect, but it's not in the same league, I don't think. And also the point you made regarding this is a very good candidate drug class for Long Covid and for a variety of conditions characterized by chronic inflammation. In fact, so many of our chronic diseases fit into that category. Well, this is fascinating, and by the way, I don't know if you know this, but we were both at Johns Hopkins at the same time when you were there in the early eighties. I was there as a cardiology fellow, but we never had a chance to meet back then.Daniel Drucker (23:41):So were you just ahead of Cricket Seidman and the whole team there, or what year was that?Eric Topol (23:46):Just before them, that's right. You were there doing, was it your internship?Daniel Drucker (23:50):I was doing an Osler internship. I think Victor McKusick loved to have a Canadian every year to recognize Osler, one of the great Canadians, and I was just lucky to get the slot that year.Eric Topol (24:04):Yeah, it's wild to have watched your efforts, your career and your colleagues and how much of a profound impact. If you were to look back though, and you were to put this into perspective because there were obviously many other hormones along the way, like leptin and so many others that were candidates to achieve what this has. Do you think there's serendipity that play out here or how do you kind of factor it all together?Daniel Drucker (24:38):Well, there there's always serendipity. I mean, for decades when people would write review articles on the neuropeptides that were important for control of hunger and satiety and appetite circuits, I would open the article, read it, and I'd say, darn, there's no GLP-1 on the figure. There's no GLP-1 or receptor on the figure, but there's leptin and agouti and the POMC peptides and all the melanocortin and so on and so forth, because physiologically, these systems are not important. As I mentioned, you don't see childhood obesity or genetic forms of obesity in people with loss of function mutations in the GLP-1 sequence or in the GLP-1 receptor. You just don't see a physiologically important effect for having low GLP-1 or having no GLP-1. And that's of course not the case for mutations in NPY or the melanocortin or leptin, et cetera.Other EffectsDaniel Drucker (25:36):But pharmacologically, it's been extraordinarily difficult to make drugs out of these other peptides and pathways that we talked about. But fortuitously or serendipitously, as you point out, these drugs seem to work and amazingly GPCRs are notoriously prone to desensitization. We use that in clinical medicine to turn off entire circuits. And thankfully what goes away with GLP-1 are the adverse effects. So nausea, vomiting, diarrhea, constipation, we see those during the first few weeks and then there's tachyphylaxis, and they generally go away in most people, but what doesn't go away through good fortune are the ability of GLP-1 to talk to those brain circuits and say, you know what? You're not hungry. You don't need to eat. You don't need to think about food. And that's just good luck. Obviously pharmacologically that's benefited all of us working in this area.Eric Topol (26:31):It's extraordinary to be able to get desensitized on the adverse effects and not lose the power of the benefit. What about addiction that is, whether it's alcohol, cigarettes, gambling, addictive behavior, do you see that that's ultimately going to be one of the principal uses of these drugs over time?Daniel Drucker (26:55):The liver docs, when I give a talk at a metabolic liver disease meeting, they say we love GLP-1 because not only might it take care of liver disease, but there are still some people that we see that are having problems with alcohol use disorders and it might also reduce that. And obviously there are tons of anecdotes that we see. If you go on social media, and you'll see lots of discussion about this, and there's a hundred or so animal paper showing that addiction related dependence behaviors are improved in the context of these medicines. But we don't have the clinical data. So we have a couple of randomized clinical trials, small ones in people with alcohol use disorder, very unimpressive data. We had a trial in people with smoking, didn't really see much, although interestingly, they noted that people drank less alcohol than they did the smoking trial. So there are dozens and dozens of trials underway now, many investigator initiated trials looking at whether it's nicotine or cocaine or cannabinoids or all kinds of compulsive behaviors. I think in the next 12 to 24 months, we're going to start to learn are these real bonafide effects that are seen in large numbers of people or are these just the anecdotes that we won't get a very good complete response. So it's really exciting neuroscience and we're going to learn a lot over the next couple of years.Eric Topol (28:20):Yeah, no, it's a fascinating area which just extends the things that we've been discussing. Now, let's say over time, over the years ahead that these drugs become because of the competition and various factors, perhaps in pill form or infrequent dosing, they become very inexpensive, not like they are today.Daniel Drucker (28:44):That'd be great speaking as a non-pharmaceutical physician.Eric Topol (28:48):Yeah, yeah, no, these companies, which of course as you well know, it accounts for the number one economy in Denmark and is having a big impact in Europe. And obviously Eli Lilly is now the most valued biopharma company in the world from all these effects are coming from this drug class, but let's just say eventually it's not expensive and the drug companies are not gouging and pleasing their investors, and we're in a different world. With all these things that we've been discussing, do you foresee a future where most people will be taking one form or another of this family of drugs to prevent all these chronic conditions that we've just been discussing independent of obesity, type 2 diabetes, the initial frontier? Do you think that's possible?Daniel Drucker (29:42):Yeah, I'm a very conservative data-driven person. So today we don't have the data. So if I was in charge of the drinking water supply in your neighborhood and I had unlimited free cheap GLP-1, I wouldn't dump it in there just yet. I don't think we have the data, but we have trials underway, as you noted for Alzheimer's disease, a challenging condition for our society with a huge unmet need if like fingers crossed, if semaglutide does show a benefit for people living with early Alzheimer's disease, if it helps for Parkinson's, if it helps for metabolic liver disease, there are also studies looking at aging, et cetera. So it's possible one day if we have a lot more data that we will begin to think, okay, maybe this is actually a useful medicine that should deserve much more exposure, but today we just don't have the data.Eric Topol (30:38):Absolutely. I couldn't agree more, but just wanted to get you kind of speculate on that a bit off script if you will, but what your thoughts were, because this will take a long time, get to that point, but you just kind of wonder when you have an absence of chronic significant side effects overall with these diverse and relatively potent benefits that cut across many organ systems and as you just mentioned, might even influence the aging process, the biologic process.Worsening InequitiesDaniel Drucker (31:10):There's another related sort of angle to this, which is that the accessibility of these medicines is very challenging even in well-developed countries, the United States, Europe, et cetera, and we have hundreds of millions of people in the global south and less well-developed economies that are also challenged by heart disease and diabetes and obesity and chronic kidney disease and liver disease. And I think we need to start having conversations and I think they are happening just like we did for HIV and just like we did for hepatitis and certainly we did very quickly for the Covid vaccines. We need to think out of the box and say we need to help people in other parts of the world who may not have access to the medicines in their current form and at their current pricing. And I think these are really important moral and ethical discussions that need to be happening now because soon we will have small molecules and the price will come down and we need to make sure it's not just people in well-developed countries that can afford access to these medicines. I think this is a great opportunity for pharmaceutical companies and the World Health Organization and other foundations to really think broadly about how we can benefit many more people.Eric Topol (32:29):I couldn't agree with you more and I'm so glad you emphasize that because we can't wait for these prices to come down and we need creative ways to bridge, to reduce inequities in a vital drug class that's emerged to have far more applicability and benefit than it was initially envisioned, certainly even 5, 10 years ago, no less 30 years ago when you got on it. So Daniel, I can't thank you enough for this discussion. Really a candid discussion reviewing a lot of the things we do know, don't know will know someday perhaps. I just want to note, I know so many people are cheering for you and your colleagues to get recognized further like by the Nobel folks in the years ahead. I think it's pretty darn likely and hopefully when we get a chance to visit again in the years ahead, we'll unravel some of the things that we discussed today that we didn't know the answers and that you as a really an authority and pioneer in the field. Also, I could admit that there's a ways to go to really understand the boundaries if there are boundaries here for how these drugs are going to be used in the years ahead.Daniel Drucker (33:51):Yeah, it's another great story for basic science and bench to bedside, and it's just another story where none of us could have predicted the outcomes that we're talking about today to their full extent. And so to the extent that we can convince our governments and our funding agencies to really fund discovery science, the benefits are never apparent immediately. But boy, do they ever come in spades later on in an unpredictable manner. And this is just a great example.Eric Topol (34:20):Yeah, I also would say that this work cracking the case of obesity, which has been a stumbling block, I ran a big trial with Rimonabant, which was a failure with the neuropsychiatric side effects and suicidal ideation that had to get dropped. And there's many others like that as you know, very well Fen-Phen, and a long list. And the fact that this could do what it's doing and well beyond just obesity is just spectacular. And what I think it does, what you just mentioned, Daniel, is the basic science work that led to this is I think an exemplar of why we should put in these efforts and not expect immediate benefits, dividends of those efforts. Because look what's happened here. If you can break through with obesity, imagine what lies ahead. So thanks so much for joining and we'll look forward to continuing to follow your work. I know you're publishing the same pace, exceptional prolific pace over many, many years, and I'm sure that's going to continue.Daniel Drucker (35:34):Well, I have a great team and so it's a pleasure me to go into work and talk to them every day.********************Thanks for listening to/reading Ground Truths.Please share if your found this podcast informative Get full access to Ground Truths at erictopol.substack.com/subscribe
Is your dog fat? If it's a Labrador, then science now provides an excuse.All dog owners know the challenge of resisting your pet's big, sad eyes as they beg for one more treat, but there is one dog breed that pushes its owners by begging more than others according to new research published this week in the journal Cell Metabolism. That dog breed is the Labrador Retriever, which was found in the study to be more likely to engage in behaviour that related to getting extra food - including begging. The scientists genetically tested 33 Labradors, of which 18 were fit and healthy, and 15 were obese. They found that the obese dogs were more likely to be carrying a variation in the gene called POMC. The variation in this gene turned off hunger cues in the dog meaning the dogs were much more food motivated and more likely to overeat. They then expanded the genetic study to include 700 more Labradors and found that the gene variation was in 23 percent or 1 in 4 of the Labs. All of the dogs that had the gene variant were also obese- and according to their owners, renowned for scavenging food and begging. To see if it was just Labradors, the researchers then studied 38 other dog breeds. They found this gene variation occurred in only one other breed - flat-coated retrievers, which are related to Labradors. The conclusion of the study was - if you own a lab and it constantly pesters you for extra treats - you as the human owner are going to need more will power to deny them if your dog is going to remain fit and healthy. LISTEN ABOVESee omnystudio.com/listener for privacy information.
We welcome the most BASED doctor out there, and a dear friend who has been on the podcast before, Dr. Abud Bakri. He's a wealth of knowledge on all things health and wellness. We dive into light environment, POMC, Testosterone, circadian biology, the deep brain structures and more. FOLLOW ABUD ON INSTAGRAM FOLLOW ABUD ON TWITTER FOLLOW ABUD ON YOUTUBE FOLLOW ABUD ON TIKTOK TIMESTAMPS: (0:00) Sunscreen and skin (1:30) Welcoming Dr. Abud Bakri (2:20) Abud's growth on Twitter (5:00) Toxic health space (6:20) Nocebo extremists (7:08) Gut health & microbiome (9:40) Circadian friendly pooping (12:25) Seasonal fermentation and variety (13:55) POMC & leptin-melanocortin pathway (17:55) Light and POMC neurons (18:50) Leptin resistance (22:45) Consequences of circadian disruption (26:00) Artificial light vs sunlight (29:35) Blue light blockers (30:35) Traditional wisdom around sunlight (33:10) Circadian friendly light (35:25) Intuitive understanding (36:50) Sleep cycles & growth hormone (40:00) Light & dark cycle (41:35) Abud's current health interests (42:45) Testosterone epidemic (45:50) Surfer to corporate spectrum (48:00) Spontaneous cancer remission (51:50) The brain (54:00) Abud 15 years from now (57:20) Educating everyday people (1:00:30) Social media and social status (1:02:30) Weak forebrains (1:07:15) Lack of masculine culture (1:10:50) Outro SPONSORS BUTCHERBOX: Choose the high-quality, sustainably sourced meat you want for FREE in every order for a year, PLUS $20 off your first box by using code 2AMPODCAST or by clicking the link here: https://shop.butcherbox.com/2ampodcast EKSTER: Get the highest quality smart wallets, dufflebags, and accessories on the market for up to 30% off using code 2AM in combination with this link here: https://shop.ekster.com/2ampodcast RAREBIRD PARAXANTHINE COFFEE: Elevate your mental wellness and cognitive health with the caffeine-like benefits of paraxanthine coffee (But without jitters, anxiety or insomnia): Use code 2AM for 20% off! https://rarebird-coffee.myshopify.com
Today, we'll be speaking with two members of a family no one wants to join. That found family is comprised of the members of the National Organization of Parents of Murdered Children and its local chapters. These members have each lost a child, sibling, relative, or even a friend to violence. Founded in Cincinnati, Ohio by Robert and Charlotte Hullinger after the murder of their daughter Lisa, this is an organization that seeks to unite and support those who have lost a loved one to homicide. Now, POMC advocates for victims' families and provides plenty of resources to help survivors.Given the recent circumstances surrounding the Delphi murders case, we wished to interview guests who can speak to the heartbreak, pain, and frustration that comes with losing someone to homicide. We were fortunate enough to get to talk with POMC National Board of Trustees President Connie Sheely and Vice President Lori King. Both joined POMC after losing a sibling to violence. They will share their thoughts on the leak of sensitive discovery documents and the ways the public, traditional media, new media, and parties in the case can behave with respect and sensitivity toward the victims families in this case. Check out the POMC's website here: https://www.pomc.org/Call the national office at: 513-721-5683.Read through the list of POMC chapters here: https://www.pomc.org/chapters/The Hobart, Indiana chapter of the POMC can be reached at: 219-616-0069 or 219-682-7285.The Kentuckiana chapter of the POMC based in Louisville, Kentucky can be reached at: 502-930-3853.Send tips to murdersheet@gmail.com.The Murder Sheet is a production of Mystery Sheet LLC .See Privacy Policy at https://art19.com/privacy and California Privacy Notice at https://art19.com/privacy#do-not-sell-my-info.
In this podcast we discuss the non-visual photoreceptor system, mealonpsin, why sunlight helps your lose weight, pro-opiomelanocortin (POMC), why building melanin is an important health strategy, and much more.Zaid K. Dahhaj is a men's health coach & co-host of The 2AM Podcast with extensive self education into the underlying drivers of chronic diseases. He has extensive knowledge of circadian biology and his current focus is on simplifying concepts surrounding our light environment and sunlight. Join my private MEMBERS Q&A Group (USD20/month)✅ https://www.skool.com/dr-maxs-circadian-resetLEARN how to optimise your Circadian Rhythm ✅ Dr Max's Optimal Circadian Health course
Fredrik Paulun er en pioner i helsearbeidet, har skrevet 23 bøker og alltid ligget foran og sett trendene lenge før andre. Nå har han gått inn i lyset og den siste boken handler om Rødlys terapi.Hør Fredriks refleksjoner om biohacking, bruk av solen og solkrem, hvordan lyset kan heale oss og være det "kosttilskuddet" som gjør deg frisk. Det heter "red light photomodulation" på biohacking språket. Lyset går inn i våre celler og jobber.Lær forskjell på infrarødt lys og rødt lys og lær hvordan energiproduksjonen fungerer. Hvordan makrofagene fungerer bedre og immunsystemet blir sterkt og blodtrykket balanseres. Lyset kan også bryte ned zombie celler (scenecent celler) som kan forynge hele systemet, man kan også få stamceller fra lys.Hva kan vi som har mørketid gjøre for heslen vår og hvordan kan vi bruke rødlyset for å forlenge dagen?Melatoninproduksjonen øker, du blir trøtt og sover bedre med nært infrarødt lys i løpet av dagen. Disse panelene kan stilles inn på flere funksjoner, mange bruker kun det røde om kvelden for å bli trette og ikke overstimulert.Hva stimulerer POMC genet, hvilket lys for å stimulere det?Hva med HRV? kan man se bruken av red light på målinger? Hva med lavt blodtrykk? Hva med pacemaker? Er det trygt?Hvor mye og ofte skal vi bruke redlight? Er mer bedre?Vi snakker om mange helsefordeler ved redlight therapy: -Huden (kviser, eksem, psoriasis, rynker, plump, cellulitter,), hva slags lys bruker vi da? -Smertelindring, hvordan virker da det røde lyset. -Reduksjon av fett på kroppen, Hva skjer med fettcellene våre under det røde lyset. -Muskler og rødt lys. -Immunsystemet, hvordan bruker vi rødt lys for å bli fortere frisk?UVB produserer D-vitamin i huden. Hva med tilskudd? Hva skjer når vi gir rødt lys terapi sammen med tilskudd av D vitamin.Vi snakker mye om dette med solkrem. Paulun forklarer hva som skjer når vi bruker solkrem og hvorfor vi ikke bør bruke det i det hele tatt. Hvordan får vi naturlig beskyttelse mot solen? Hvorfor vi ikke skal spise vegetabilske oljer?Hva skal vi se etter når vi skal kjøpe ett rød lys panel? Hvordan vet vi at det vi kjøper er trygt og gjør det som blir lovet?Hvor langt unna panelet skal vi sitte? Må vi bruke briller?Nutrilight er selskapet Paulun jobber med ,og er med på å utvikle produkter.Vi avslutter med en cliffhanger, så følg med. SORT LYSBoken: Ljusrevolusjonen: https://www.adlibris.com/no/sok?filter=author%3AFredrik%20Pauluninstagram: https://www.instagram.com/fredrikpaulun/Red Light paneler: https://nutrilight.seBiohacking Weekend: Fredrik Paulun kommer og holder foredrag på Biohacking Weekend. Her kommer det masse nytt så gled derehttps://www.kongresspartner.no/no/biohacking-weekend-one-day-event-2024Studien Paulun referer til på Svenske kvinner:https://www.kongresspartner.no/no/biohacking-weekend-one-day-event-2024
Sunlight, the POMC gene, shitty-quality chicken, and more! TIMESTAMPS: (0:00) Sponsors (2:00) A round of applause (3:00) Tustin hangar fire (7:40) Shoutout to mothers (10:50) Maternal intuition (13:00) Sunlight, POMC, & endogenous peptides (15:50) Artifical light raising blood sugar & insulin (18:30) Epigenetics and human behavior (22:00) Numerology (24:00) Odd dreams (25:00) Jacket season (26:30) Appetite & resistance training (28:20) Urine therapy (30:00) Disgusting conventional chicken (33:00) Uring therapy routine (34:30) Raw meat health gurus (36:00) Vegetable oil (37:20) The McChicken theory (41:50) The 2AM ranch (43:30) Outro SPONSORS: RAREBIRD PARAXANTHINE COFFEE: Elevate your mental wellness and cognitive health with the caffeine-like benefits of paraxanthine coffee (But without jitters, anxiety or insomnia): Use code 2AM for 20% off! https://rarebird-coffee.myshopify.com?sca_ref=3811815.rHP27MxI90 VITAL RED LIGHT: Experience the healing power of red and infrared light therapy to rejuvenate your skin, mind, and body: Use code 2AM for 15% off! PORTAL: Finally get the sleep you've dreamed of with scientifically backed ingredients from Portal. It'll blow your mind. Use the link and code 2AM for 10% off: www.withportal.com/2AM EKSTER: Get the highest quality smart wallet on the market for up to 30% off using code 2AM in combination with this link here: https://shop.ekster.com/2ampodcast FOLLOW THE 2AM PODCAST: ALL PLATFORMS
Robert and Charlotte Hullinger, from Cincinnati, OH, formed Parents of Murdered Children after their 19 year old Daughter Lisa was brutally attacked by her ex boyfriend and died from her injuries on September 25th, 1978 in Hamburg, Germany while there on a work study program. 20 years later Gloria Gomez was murdered the same way….by the same guy.In 2007, Congress designated September 25 as the National Day of Remembrance for Murder Victims. The purpose of this event is to focus on the impact of murder on families, and communities, and ways to support and serve survivors.Today we'd like to honor the memories of Lisa and Gloria.If you are going through the horrific and traumatic experience of losing a child to murder and need resources, you can go to https://pomc.org/resources-2/ or https://globaljusticerc.org/parents-of-murdered-children/ They provide the on-going emotional support needed to help parents and other survivors facilitate the reconstruction of a “new life” and to promote a healthy resolution. Not only does POMC help survivors deal with their acute grief but also helps with the criminal justice system.Get your Merch here https://belleame-creations.square.site/shop/judgy-crime-girls/2Sources: http://kidnappingmurderandmayhem.blogspot.com/2008/05/forgetting-lisa-forgetting-gloria.html https://caselaw.findlaw.com/court/fl-supreme-court/1126117.html Support the showThanks for listening! Subscribe here: For Bonus Friday Episodes! (You'll also get a shout out on the show, a handwritten thank you from your ladies, and 20% off our merch! Follow us on Instagram, TikTok and Facebook.
Dr Jalal Khan is one of Australia's leading quantum health clinicians as well as a practicing dentist. In this fascinating conversation we cover Jalal's thoughts on the centrality of circadian biology to health, why diet-only health paradigms lack the complete picture, role of mitochondrial dysfunction and disease, pro-opiomelanocortin (POMC), melanin and much more. TIMESTAMPS00:01:39 What is Quantum health & circadian biology?00:07:07 How is food just a form of light? The effect of unseasonal eating on your mitochondria00:14:00 Why carnivore and animal based diets work: reducing deuterium00:15:45 Dr Max: Contribution of fruit to metabolic syndrome is dependent on latitude and circadian regulation00:21:10 Invitation for practitioners to consider the context of their patients when reversing disease00:23:35 What is deuterium?00:29:40 Understanding mitochondrial heteroplasmy and mitochondrial dysfunction00:35:30 Mitochondria as environmental light sensors, the need for UV light for our biology00:45:30 The essential role of melatonin00:49:00 Pro-opiomelanocortin (POMC) is the master regulator of energy metabolism00:57:40 Dr Max: theme park ticket analogy of POMC and its evolutionary history01:04:20 Melanin allows us to harvest energy from UV light01:08:00 The incredible functions of melanin in biology01:16:45 Reflections on the recent REGNERATE health summit, preview of upcoming Quantum Health SummitLINKSA mitochondrial bioenergetic etiology of disease by Dr Doug Wallace- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3614529/60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH https://pubmed.ncbi.nlm.nih.gov/26939593/Melanin, the Master Molecule by Arturo Solís Herrera- https://benthambooks.com/book/9781681086538/Jack Kruse Series on Regenerative Health Podcasthttps://www.youtube.com/playlist?list=PLrv4qp8WwfQFHxy3WDCAOiy-WZiwrG2tiFollow Dr KhanDr Khan's website: https://www.k2calibre.com/Quantum Health Summit - https://wolkifarm.com.au/product/quantum-health-summit/
Sunscreen: Unknown Death Causers Part 2 | Improvement Warrior Podcast Episode 36 Podcast show notes/resources at http://www.improvementwarriorfitness.com/sunscreen Highlights for sunscreen: unknown death causers part 2 | Episode 36 The history of sunscreen and lighter vs. darker skin Why humans do not need sunscreen at all How to build a solar callus to be able to be out in the sun without burning Why & how a solar callus is not just about solar exposure Why Red light from the sun is vital to health and skin protection What is your redox potential and why should you care What you need to know about sunscreen and vitamin D Why melanin, both visible and non-visible, is our super power How sunscreens actually block UV light and why its bad Why & how paleness is an indication of poor health Why circadian nutrition, aka eating seasonally is critical for skin and overall health. Why heteroplasmy is one of the most important factors for health and what it is. The case for why UV is vital to life and why you probably need more (unblocked, of course) The case for why UV light does NOT cause skin cancer The things we have inside our cells to help us absorb UV light The case for why artifiicial blue light does cause cancer Why women tend to lose their health quicker than men Where in the world is the highest rate of melanoma and why What is histadine and how does it relate to histamine and why you never want to use an anti-histamine Why DHA helps you build a solar callus and your overall health Why our mitochondrial water ‘stores' sun's energy for later use What a sunburn tells you and why it is not bad or does not cause cancer How UVA and UVB created melanin work in your body and why melanin is your natural sunscreen Sunscreen hurts our endocrine system and why that hurts our hormones and growth, development and metabolism How UV makes POMC and why you should care How sunscreens increase free radicals How sunscreens increase the excited state of our atoms and why that is really bad. Why melanin is supposed to transform UV light into this harmless, but needed 'substance' What are the worst sunscreen ingredients The 5 biggest issues with sunscreen How our body creates UVC light which is said to be blocked by our atmosphere How sunlight works with our circadian rhythm and mechanisms on a seasonal basis. How melanopsin, our blue light detector, helps skin, eye and overall health Why Polar Bears don't freeze to death and why humans cannot tolerate cold And much more..... Hope you enjoy the show. Please share it out to any friends or anybody having issues with their health. And of course don't forget to rate the podcast on apple podcasts. Stay Strong, Stay Positive, Be the Improvement Warrior To support the podcast please either leave a 5-star review on Itunes here, visit the links and sponsors of the show, You can also support me via Patreon, Paypal or through my podcast hosting company, Anchor. Paypal Support: https://www.paypal.com/paypalme/yuntraining Anchor Support: https://anchor.fm/improvementwarriorpodcast/support Patreon Supporter: https://www.patreon.com/join/improvementwarrior? Listen/Watch Previous Episodes of Improvement Warrior Podcast Here. --- Support this podcast: https://podcasters.spotify.com/pod/show/improvementwarriorpodcast/support
As part of our MrBallen Foundation series, we have Bev Warnock, the executive director of Parents of Murdered Children, an organization dedicated to supporting families devastated by the unimaginable loss of a loved one to violence. As I spoke with Bev, I couldn't help but feel the weight of her mission. The pain and grief that these families endure is unfathomable. But within that darkness, Parents of Murdered Children brings a glimmer of hope, a lifeline for those navigating the turbulent waters of grief. The organization's origins trace back to a tragic incident in 1978 when a young woman's life was cut short by the hands of her ex-boyfriend. From this heart-wrenching loss emerged a gathering of parents who, like broken pieces, found strength in coming together. And thus, Parents of Murdered Children was born, offering solace, compassion, and a sense of belonging to those who've walked this unimaginable path. In this episode, Bev shares the struggles these families face – the legal battles, the lingering questions of why, and the challenge of rebuilding lives while never letting go of precious memories. She tells us about the profound importance of remembering those lost, and how even the simplest acts of remembrance can comfort a grieving heart. But it's not just the families that bear the weight of grief; the entire community also suffers. Bev talks about how parents struggle to cope with their grief while helping their surviving children navigate their pain. It's a heartbreaking balance that requires understanding and support from everyone around them. So, as we delve into this episode of All-Volunteer, All Heart, let us remember the strength and courage of those facing unimaginable heartbreak. And may we all be inspired to reach out, listen, and remember the stories of those who may no longer be with us but whose memories will forever be cherished in the hearts of those they left behind. Bev and Susan gave a few challenges and action items in this episode: Reach out to someone who has lost a loved one and share a favorite memory or story about the person. Let them know that their loved one is not forgotten and that their memory lives on in the hearts of others. Encourage friends and family members to be patient and understanding with grieving parents or loved ones. Offer a listening ear and let them express their emotions without judgment or pressure to move on. Challenge yourself to attend a support group or grief workshop if you have experienced the loss of a loved one to violence. Connecting with others who have gone through similar experiences can be a crucial step in the healing process. Consider volunteering or supporting organizations like Parents of Murdered Children that provide vital resources and support to families affected by violence. Your contribution, whether big or small, can make a significant difference in someone's life. Be mindful of the impact of domestic violence and strive to raise awareness about its devastating consequences. Support initiatives that address and prevent violence within communities, as fostering a safe and nurturing environment is essential for everyone's well-being. Links from this episode: POMC.org MrBallen Foundation Binky Patrol Comforting Covers for Kids
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.18.549357v1?rss=1 Authors: Chen, H.-J. C., Yang, A., Mazzaferro, S., Mali, I., Cahn, O., Kentistou, K., Rowley, C., Stewart, N., Seah, J. W. E., Pisupati, V., Kirwan, P., Aggarwal, S., Toyohara, T., Florido, M. H. C., Cowan, C. A., Quambusch, L., Hyvonen, M., Livesey, M. R., Perry, J. R. B., Marioni, J. C., Merkle, F. T. Abstract: Obesity substantially increases the risk of type 2 diabetes, cardiovascular disease, and other diseases, making it a leading preventable cause of death in developed countries. It has a strong genetic basis, with obesity-associated genetic variants preferentially acting in the brain. This includes the hypothalamic pro-opiomelanocortin (POMC) neurons that inhibit food intake and are stimulated by drugs that agonise glucagon-like 1 peptide receptor (GLP1R) including Semaglutide (Ozempic/Wegovy). We therefore hypothesised that drugs which selectively activate human POMC neurons would suppress appetite and promote weight loss, and that focusing on drugs already approved for use would facilitate rapid clinical translation. We therefore generated POMC neurons from human pluripotent stem cells (hPSCs) and identified enriched genes that were genetically associated with obesity and targeted by approved drugs. We found that human POMC neurons are enriched in GLP1R, reliably activated by Semaglutide, and their responses are further increased by co-administration of Ceritinib, an FDA-approved drug potently and selectively inhibiting anaplastic lymphoma kinase (ALK). Ceritinib reduced food intake and body weight in obese but not lean mice, and upregulated the expression of GLP1R in the mouse hypothalamus and hPSC-derived human hypothalamic neurons. These studies reveal a new potential therapeutic strategy for reducing food intake and body weight, and demonstrate the utility of hPSC-derived hypothalamic neurons for drug discovery. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.07.11.548551v1?rss=1 Authors: Zhang, S. X., Kim, A., Madara, J. C., Zhu, P. K., Christenson, L. F., Lutas, A., Kalugin, P. N., Jin, Y., Paul, A., Tian, L., Lowell, B. B., Andermann, M. L. Abstract: We investigated how transmission of hunger- and satiety-promoting neuropeptides, NPY and alpha MSH, is integrated at the level of intracellular signaling to control feeding. Receptors for these peptides use the second messenger cAMP, but the messenger's spatiotemporal dynamics and role in energy balance are controversial. We show that AgRP axon stimulation in the paraventricular hypothalamus evokes probabilistic and spatially restricted NPY release that triggers stochastic cAMP decrements in downstream MC4R-expressing neurons (PVHMC4R). Meanwhile, POMC axon stimulation triggers stochastic, alpha MSH-dependent cAMP increments. NPY and alpha MSH competitively control cAMP, as reflected by hunger-state-dependent differences in the amplitude and persistence of cAMP transients evoked by each peptide. During feeding bouts, elevated alpha MSH release and suppressed NPY release cooperatively sustain elevated cAMP in PVH MC4R neurons, thereby potentiating feeding-related excitatory inputs and promoting satiation across minutes. Our findings highlight how state-dependent integration of opposing, quantal peptidergic events by a common biochemical target calibrates energy intake. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
In this podcast episode, we hear from ISSA's own team members and bootcamp co-hosts Jenny Scott and John Bauer for our first edition of Lighting Fitness Facts and Trainer REAL talk. In this episode Jenny and John shed light on the latest scientific research and evidence-based information in the world of health and fitness, exploring fascinating studies and discoveries that can revolutionize the way we approach our well-being.In our first round of questions, Jenny and John dive into intriguing findings that uncover the mysteries behind our appetite, exercise motivation, cell metabolism, resistance training, and more. They then move into the Training Real Talk segment where they discuss strategies for making health cool and promoting scientific literacy in the fitness world. Discover how to prioritize your health, access reliable sources of information, understand basic science concepts, and seek guidance from experts!References from this episode: References for show notes:Yue Qi, Nicola J. Lee, Chi Kin Ip, Ronaldo Enriquez, Ramon Tasan, Lei Zhang, Herbert Herzog. Agrp-negative arcuate NPY neurons drive feeding under positive energy balance via altering leptin responsiveness in POMC neurons. Cell Metabolism, 2023; DOI: 10.1016/j.cmet.2023.04.020Leandro Garcia, Matthew Pearce, Ali Abbas, Alexander Mok, Tessa Strain, Sara Ali, Alessio Crippa, Paddy C Dempsey, Rajna Golubic, Paul Kelly, Yvonne Laird, Eoin McNamara, Samuel Moore, Thiago Herick de Sa, Andrea D Smith, Katrien Wijndaele, James Woodcock, Soren Brage. Non-occupational physical activity and risk of cardiovascular disease, cancer and mortality outcomes: a dose–response meta-analysis of large prospective studies. British Journal of Sports Medicine, 2023; bjsports-2022-105669 DOI: 10.1136/bjsports-2022-105669Dohnalová, L., Lundgren, P., Carty, J.R.E. et al. A microbiome-dependent gut–brain pathway regulates motivation for exercise. Nature, 2022 DOI: 10.1038/s41586-022-05525-zWeakley, J., Schoenfeld, B.J., Ljungberg, J. et al. Physiological Responses and Adaptations to Lower Load Resistance Training: Implications for Health and Performance. Sports Med - Open 9, 28 (2023). https://doi.org/10.1186/s40798-023-00578-4
Dr Peter Walsh joins me to talk all things polycystic ovary syndrome (PCOS), how and why it develops, the role of processed food, stress, visceral fat, endocrine disrupting chemicals and much, much more. Dr Peter Walsh is a GP and metabolic practitioner from Melbourne, Australia with a special interest in Polycystic ovary syndrome and female reproductive health. He uses a holistic approach to restoring fertility using low carbohydrate and carnivore dietary approaches. He consults out of Yarra Trail Medical Centre (see below for links). TIMESTAMPS00:00:34 Dr Walsh's background00:03:02 What is Polycystic ovary syndrome (PCOS)?00:05:32 Why Dr Walsh calls PCOS ‘Type 4 diabetes'00:12:19 Diagnosing PCOS00:18:34 Environmental endocrine disruptors in normal weight women with PCOS00:22:44 The contribution of seed oils to epidemic of PCOS00:25:18 How soon can fertility return with lifestyle change?00:29:04 Normalising metabolic health as a strategy for optimizing fertility00:30:25 Could endometriosis be related to metabolic disease? 00:34:26 Stress and cortisol driving visceral fat and PCOS00:44:34 Leptin resistance and the effect of blue light toxicity and artificial light after dark00:49:04 The flawed mainstream approach to PCOS00:58:05 Reversing PCOS takes a holistic approach is necessary00:59:50 Markers of optimal fertility and Dr Walsh's approach01:05:34: Dr Walsh's take on regenerative farming01:09:55 Closing thoughts from Dr WalshLINKSDr. Peter Walsh - 'Polycystic Ovarian Syndrome - Type 4 Diabetes' Low Carb Down Under https://www.youtube.com/watch?v=mUsRZ310IgEDr Jack Kruse: LIGHT, melanin, POMC in human evolution & disease | Regenerative Health Podcast #21 https://www.youtube.com/watch?v=Ln3WszTq0uAHold on to Your Kids: Why Parents Need to Matter More Than Peers by Gabor Maté & Gordon Neufeldhttps://www.amazon.com.au/Hold-Your-Kids-Parents-Matter/dp/178504219XFollow DR PETER WALSHYarra Trail Medical, Melbourne - https://www.yarratrailmedical.com.au/Keeto Fertility - https://www.keetofertility.com/Email: reception@yarratrailmedical dot com dot auFollow Dr MAXTwitter: @mgulhaneMDInstagram: @dr_max_gulhaneLinktree: https://linktr.ee/maxgulhanemd
Obesity is a chronic disease and is associated with related conditions such as cardio vascular disease(heart attack and stroke),type 2 diabetes, and certain cancers. The current understanding of obesity demonstrates both biological and environmental factors like economics and infrastructure, psychosocial and developmental issues as important contributors as well as newer understanding of their role in influencing the hypothalamus. New treatment strategies and medications demonstrate opportunities for success in management of obesity. Guest: Joshua Thaler, MD, PhD. Associate Professor of Medicine, Division of Metabolism, Endocrinology and Nutrition. Dr. Thaler graduated with a major in Biochemistry from Harvard College (Magna Cum Laude with Highest Honors, and on the Dean's List), then obtained an MD and a PhD in Biomedical Sciences from the University of California, San Diego and the Salk Institute (where he was a Chapman Scholar and a Lucille P. Markey Fellow). He short-tracked through the Internal Medicine residency program at UW and was an endocrinology/metabolism fellow, working in Dr. Michael Schwartz's laboratory. He is currently an Associate Professor at the UW Diabetes Institute. Research Interests Dr. Thaler's focus is the hypothalamic regulation of energy homeostasis and the alterations to this system during obesity pathogenesis. His primary project investigates hypothalamic inflammation and its relationship to high fat diet-induced weight gain with an emphasis on the role of glial cells (astrocytes and microglia) in modulating the neuronal regulation of energy homeostasis. In particular, his research aims to determine whether glial cells provide a repair response to diet-induced damage to critical hypothalamic neurons and whether interventions targeted at glia may therefore influence the course of obesity. A second study examines the role of inflammatory signaling in hypothalamic neurons and microglia in obesity-associated insulin resistance and diabetes. Additionally, Dr. Thaler's research is examining the metabolic role of POMC neurons through modification of atypical protein kinase C signaling. During This Episode We Discuss: Obesity versus being overweight, what Body Mass Index (BMI) defines each condition. Causes of obesity. New data on root causes Health impact of obesity The individualized approach to treating obesity Investigations and Research into the role of the brain (Hypothalamus) in obesity and obesity management. Successful strategies for managing obesity,including newer medications and Bariatric Surgery Quotes (Tweetables): The US obesity prevalence was 41.9% in 2017-March 2020 BMI 25-30 = overweight BMI 30 or greater = Obesity “Obesity by many estimates is at least 50% if not more based on inherited genes. That susceptibility is being acted on by the environment, You shouldn't take the fatalistic view I've got these genes and there is no hope” Dr Josh Thaler “The Heavier you are, the higher your energy expenditure. Thus we can't say that in general, that people who are overweight have a slower metabolism” Dr Josh Thaler “How much weight needs to be lost in order to reverse either the disease that's established or lower the risk of the one that hasn't come yet.. You don't have to go back to your original normal weight..What the data suggests is that even 5-10% weight loss from wherever your current weight,is sufficient to reverse a lot of things(associated diseases) that are associated with obesity” Dr Josh Thaler “The (newer injectable)weight loss medications do not cure (obesity), if you stop them, the weight will come back…there is no reason to believe it changed your biology in some way that's permanent” Dr Josh Thaler Recommended Resources: CDC https://www.cdc.gov/obesity/basics/index.html Obesity Canada ( formerly called,The Canadian Obesity Network). Obesitycanada.ca. The Obesity Society www.obesity.org. Ania Jastreboff, MD, PhD Kevin D.Hall, PhD Multiple You Tube videos and publications Michael W. Schwartz, MD University of Washington
Dr Jack Kruse joins me in an epic three-hour interview to weave the story of human evolution fundamentally tied to light. He describes our transition from furry ground dwelling mammals to upright walking primates, the critical role of the POMC gene, melanin and function of mitochondria as producers of endogenous light, as well as the distortion of the light environment as the key underlying driver of modern chronic disease.Dr Jack Kruse is a neurosurgeon, biophysicist, health optimisation researcher and founding father of the circadian health / mitochondrial medicine movement. This is the first in a series of interviews with Dr Kruse that will also cover water and magnetism, two further installments in a trilogy that strongly challenges the centrality of diet as the chief determinant of optimal health. Stay tuned for further episodes. *This is not a podcast for beginners, and if you want the cliff notes I'd suggest watching Dr Max's summary takes and the closing thoughts. Some explicit language in this interview – Dr Jack is extremely passionate!TIMESTAMPS00:00:00 Dr Max's intro00:05:11 Dr Kruse's backstory00:10:22 Differences between centralized and decentralized medicine00:12:32 Incongruence in Darwin's theories of evolution00:13:27 Evolution of mammals from ground dwelling creatures00:17:57 The POMC gene and its cleavage products allowed mammals to survive the dinosaur extinction event00:28:12 POMC, the leptin melanocortin pathway and human metabolism00:34:37 POMC and autoimmunity00:38:42 To understand the effect of light on biology, we need to understand physics00:41:15 UV light from the sun is critical to stimulating POMC00:46:42 Robert O. Becker's research on bioelectrics and cellular DC electric current00:50:22 POMC, melanin and biological semi-conductors00:59:52 Dr Max's summary of the first hour01:05:05 What is leptin and its function?01:12:28 All mammalian cells generate UV light in the mitochondria and use it to signal01:19:27 The biological function of melanin01:26:19 Dr Max's summary of the function of leptin01:30:05 Reversing vitiligo, grey hair & melanin loss with sun & UV light01:36:43 Melanoma develops in absence of full spectrum (red/infrared) sunlight01:39:38 Dr Max's summary of the first 1.5 hours01:41:22 What are mitochondria?01:47:29 Competing theories on the factors that influenced development of human brain01:49:27 History of biological semi-conductors and importance of DHA in the SN2 position01:56:36 Photoreceptors, neuropsin and mental health conditions 02:08:00 Incongruent light signals between eye and skin creates disease02:12:47 The harms of taking exogenous melatonin02:17:52 Why blocking UV light causes melanoma02:24:32 Rebuttals to ‘light causes all diseases' point of view02:38:42 Understanding light is critical to understanding the root causes of patients diseases02:54:03 Dr Kruse's take on premature male pattern balding and refractory error aka ‘soyjak meme'02:59:49 Why we see low serum Vitamin D in overweight or obese people03:04:49 Dr Jack's closing thoughts03:08:02 Three actionable steps for the listener FURTHER READINGSee Youtube show notes for full list - unable to fit here
La Dra. Julia María Lesher Gordillo, Profesora Investigadora de la División Académica de Ciencias Biológicas de la UJAT, nos habla sobre su proyecto: Metilación en el gen POMC en la ruta de glucocorticoides y el gen SOX9 de determinación sexual, en poblaciones de Manatíes (Trichechus manatus manatus) en poblaciones sujetas a estrés ambiental estacional. --- Send in a voice message: https://podcasters.spotify.com/pod/show/ciencia-y-tecnologa-ujat/message
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.02.28.530282v1?rss=1 Authors: Kuang, D., Hanchate, N. K., Lee, C.-Y., Heck, A., Ye, X., Erdenebileg, M., Buck, L. B. Abstract: The sense of smell has potent effects on appetite, but the underlying neural mechanisms are largely a mystery. The hypothalamic arcuate nucleus contains two subsets of neurons linked to appetite: AgRP (agouti-related peptide) neurons, which enhance appetite, and POMC (pro-opiomelanocortin) neurons, which suppress appetite. Here, we find that AgRP and POMC neurons receive indirect inputs from partially overlapping areas of the olfactory cortex, thus identifying their sources of odor signals. We also find neurons directly upstream of AgRP or POMC neurons in numerous other areas, identifying potential relays between the olfactory cortex and AgRP or POMC neurons. Transcriptome profiling of individual AgRP neurons reveals differential expression of receptors for multiple neuromodulators. Notably, known ligands of the receptors define subsets of neurons directly upstream of AgRP neurons in specific brain areas. Together, these findings indicate that higher olfactory areas can differentially influence AgRP and POMC appetite neurons, that subsets of AgRP neurons can be regulated by different neuromodulators, and that subsets of neurons upstream of AgRP neurons in specific brain areas use different neuromodulators, together or in distinct combinations to modulate AgRP neurons and thus appetite. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Today we're going to talk about a question I get often. How do I know if I need weight-loss medication? Unfortunately, the answer isn't simple, and many factors must be considered. The first step is to talk with your primary care physician to rule out certain health conditions (e.g., hypothyroidism, Cushing's disease, and PCOS) or medications (e.g., steroids, antidepressants, and beta blockers) that can contribute to excess weight. It's a good idea to rule out these possibilities before starting a weight-loss medication. Then your provider can help you set realistic weight goals and help you make changes to your diet. You can also get help increasing your physical activity and monitoring for any weight-related health risks (e.g., high blood pressure, joint pain, and type 2 diabetes). When these lifestyle changes (diet and exercise) aren't enough for you to lose the weight you desire, weight-loss medications like semaglutide may be helpful. It's important to remember that obesity is a chronic, complicated medical condition. And it's difficult to manage. When a person has excess body fat, they're at risk for many health problems like high blood pressure, type 2 diabetes, stroke, heart disease, high cholesterol, depression, anxiety, fertility issues, joint and muscle pains, sleep and energy problems, erectile dysfunction, and several types of cancer. The fact of the matter is people with obesity die younger than people who do not have obesity. It's also important to keep in mind that even when taking weight-loss medications like semaglutide, you must continue to eat healthy and exercise regularly to maintain long-term weight loss. What causes obesity (weight gain)? When it comes to weight gain, most people know that obesity can be caused by eating too many calories and not exercising enough. But the fact is that a complex interaction of our genes and hormones with our environments causes obesity. Scientists have been studying how our genes and hormones affect our weight for years. Researchers have studied leptin levels, POMC gene mutations, testosterone and estrogen levels, and cortisol levels. Also, lack of sleep, stress, and an unhealthy gut microbiome can lead to weight gain. Too little sleep leads to higher levels of ghrelin (a gut hormone that stimulates appetite) and lower levels of leptin (a hormone released by your fat cells that suppress your appetite). When we're stressed, our bodies release cortisol (the stress hormone). Short-term, this hormone helps to increase our heart rate, blood pressure, and blood sugar. But, with repeated stress, over time, you begin to feel tired, and depressed and experience weight gain. An unhealthy gut microbiome can affect how you store fats and absorb nutrients from your food, making it harder to maintain a healthy weight. Like lack of sleep, an unhealthy gut may also increase the amount of ghrelin, causing you to feel hungry, which may lead to weight gain. How can I improve my sleep, stress levels, and gut health? Last week I briefly talked about ways to improve your sleep environment by avoiding technology, caffeine, and alcohol before bed. Other tips to improve sleep are to use your bedroom for sleep and intimate activities only (avoid watching television, reading books, and working on your computer), have a consistent bedtime and wake time, and keep your bedroom dark and at a comfortable temperature. Stress can come from all types of life events (e.g., work, death of a friend or family member, divorce, childbirth). What is stressful for one person may not be stressful for someone else. Depending on our current situation, certain things can make us more sensitive to life's stresses (e.g., financial situation, health situation, support system at home). But one thing is certain: decreasing stress can help reduce the effects that stress can have on our minds and bodies. Engaging in regular physical activity, if able, practicing meditation, spending time with friends or family, getting quality sleep, talking to a therapist, and eating healthy food can help relieve the effect of stress. I've talked about gut health in the context of BPC 157. But as a refresher, you can improve your gut microbiome by eating a diverse range of foods, particularly high-fiber foods like broccoli and lentils and foods rich in polyphenols (e.g., whole grains and dark chocolate). You also should limit your intake of artificial sweeteners and take antibiotics only when necessary. You may also want to consider talking to your healthcare provider about taking a daily probiotic to help reduce gut inflammation and encourage "good" bacteria to grow if you continue to have stomach pain, cramping, gas, or bloating. Thanks again for listening to The Peptide Podcast. You can find more information at pepties.com. We love having you as part of our community. If you love this podcast, please share it with your friends and family on social media. Have a happy, healthy week! Pro Tips We're huge advocates of using daily collagen peptide supplements in your routine to help with skin, nail, bone, and joint health. But what do you know about peptides for health and wellness? Giving yourself a peptide injection can be scary or confusing. But we've got you covered. Check out 6 tips to make peptide injections easier. And, make sure you have the supplies you'll need. This may include syringes, needles, alcohol pads, and a sharps container.
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In this podcast Dr. Rodney and Karen talk about the health and longevity benefits of cold exposure. This practice definitely gets most of us out of our comfort zone. Here are a few of the reasons to give it a try:1. Raises your metabolic rateThis has to be one of the most compelling because cold exposure increases your BAT - Brown Adipose Tissue which in turn increases your metabolic rate. That means you can eat more without gaining weight and have more energy. 2. Improves fat burningCold exposure ramps up fat burning as the body makes the attempt to keep your body warm. Some have even called it a "weapon" to combat obesity. Are you ready to turn the thermostat down a few degrees?3. Boosts glycemic control and insulin sensitivityWhen you activate BAT it can increase blood glucose so that it is burned as fuel or stored as glycogen (for use later) rather than fat. When insulin sensitivity goes up it improves metabolic health and has an anti-diabetic effect. 4. Diminishes inflammation and painCold exposure is often used to alleviate musculoskeletal pain and inflammation in conditions like arthritis and fibromyalgia. In one study, participants with inflammatory arthritis who took a two-minute cold shower each day for a week experienced significant reductions in pain. Cold exposure leads to vasoconstriction and reduces blood flow, which in turn reduces inflammation in tissues within and around injured sites. 5. Boosts moodResearchers believe these beneficial effects may be tied to cold exposure initiating an endocrine response and increasing hormones like cortisone, epinephrine, norepinephrine, adrenocorticotropic hormone (ACTH), pro-opiomelanocortin (POMC),and endorphins. On top of that, cold exposure may activate the body's own pain control system.6. Promotes better sleep qualityCooler temperatures (between 60 and 67°F) help lower core temperature, which facilitates sleep. Also, body temperature is a strong driver of circadian rhythms. In fact, similar to light, temperature is one of the environmental cues that's able to reset the body's circadian clocks. Turn down the thermostat or take a cold shower.7. Raises alertness & sharpens focusA cold shower can wake you and your body up, promoting a higher state of alertness. The cold also stimulates deeper breathing, helping increase oxygenation of the body's tissues.8. Builds resilienceAs you get acclimated to the cold your stress response (fight or flight) is blunted after repeated exposure. This is what hormetic stress is all about—exposure to small, transient stress leads to adaptation. This improved stress tolerance applies then to other areas of life through greater willpower and remaining cool-headed.9. Enhances cognitive functionConsidering the benefits on hormones (both stress & feel-good chemicals) and the enhancement in resiliency, it should not surprise you that cold exposure can also be good for the brain leading to better brain function. Repeated cold exposure is likely to be beneficial and neuroprotective because it regulates the release of inflammatory cytokines and nitric oxide.10. Connects to your true selfCold exposure therapy builds mental toughness and provides a place where your worries disappear. As you learn to control your breathing your mind clears and focus ensues. You just might also find yourself.Get started with cold exposure:Turn down the thermostatCold and contrast showersCold-water immersion (e.g., cold pools, ice baths, etc.)Go outside in cold temperaturesFollow us on Instagram and Facebook.
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.18.516150v1?rss=1 Authors: Ursem, S. R., Diepenbroek, C., Kool, T., Eggels, L., Heijboer, A. C., la Fleur, S. E. Abstract: Fibroblast growth factor 23 (FGF23) is a key regulator of systemic phosphate homeostasis, but also an interplay with glucose metabolism has been suggested. Several studies implicate a function of FGF23 in the brain, and indeed we have recently identified FGF23 protein in several brain areas in rats, such as the hypothalamus, third ventricle and choroid plexus. In the current study, we aimed to determine the effect of an intracerebroventricular (icv) injection of FGF23 in the third ventricle of rats on hypothalamic genes involved in glucose regulation. In addition, we assessed whether glycerol can be used safely for icv injections as glycerol is used as a stabilizing compound for FGF23 protein. Adult Wistar rats received an icv injection of recombinant rat FGF23 or vehicle. Dose dependent behavioral changes, suggestive of stress, were observed directly after infusion of FGF23. After 60 min animals were sacrificed and the arcuate nucleus, lateral hypothalamus and choroid plexus were isolated. In these brain regions gene expression was determined of the FGF23 receptor complex (FGFR1, Klotho), NPY, POMC, phosphate transporters (SLC20 and SLC34 families) and markers of cellular ER stress (ATF4 and the ratio of spliced/unspliced XBP1). We showed that glycerol is well tolerated as stabilizer for icv injections. In FGF23-treated animals, cellular ER stress markers were increased in the arcuate nucleus. FGF23 injection did not affect expression of its receptor complex, NPY, POMC, or phosphate transporters. Future studies are warranted to investigate the effect of FGF23 in the brain on the protein level and on neuronal activation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.09.09.507267v1?rss=1 Authors: Nagpal, J., Eachus, H., Lityagina, O., Ryu, S. Abstract: Organisms respond to stressors through a coordinated set of physiological and behavioural responses. Zebrafish provides an opportunity to study conserved mechanisms underlying the stress-response that is regulated largely by the neuroendocrine Hypothalamus-Pituitary-Adrenal/Interrenal (HPA) axis, with glucocorticoids (GC) as the final effector. In this study, we evaluated the effect of chronically active GC signalling in early life on the baseline and stress evoked GC(cortisol) levels in larval zebrafish. To this end, we employed an optogenetic actuator, Beggiatoa photoactivated adenylyl cyclase, expressed in the interrenal cells of zebrafish and demonstrate that its chronic activation leads to hypercortisolaemia and dampens the acute-stress evoked cortisol levels, across a variety of stressor modalities during early life. This blunting of stress-response, a phenotype reported by many studies to be observed in human subjects exposed to early-life trauma, was conserved in ontogeny at a later developmental stage. Furthermore, we observe a strong reduction of proopiomelanocortin (POMC)-expressing cells in the pituitary as well as global upregulation of FKBP5 gene expression, impinging on the negative feedback regulation elicited by elevated cortisol levels. Going forward, we propose that this model can be leveraged to tease apart the mechanisms underlying developmental programming of HPA axis by early-life stress and its implications for vulnerability and resilience to stress in adulthood. Copy rights belong to original authors. Visit the link for more info Podcast created by PaperPlayer
Ask a Doctor - What Your Doctor Wants You to Know with Dr. Virgie
In this information-packed episode, award-winning obesity medicine specialist Dr. Fatima Cody Stanford discusses new research and destroys old myths about the diseases of overweight and obesity. Dr. Stanford explains science that shows our DNA determines how much we weigh more than how tall we are, the two brain pathways - POMC and AgRP - that regulate why some of us store more fat than others despite ingesting fewer calories, and the most recent effective weight loss medication weapons added to the obesity-fighting arsenal.
Ask a Doctor - What Your Doctor Wants You to Know with Dr. Virgie
In this information-packed episode, award-winning obesity medicine specialist Dr. Fatima Cody Stanford discusses new research and destroys old myths about the diseases of overweight and obesity. Dr. Stanford explains science that shows our DNA determines how much we weigh more than how tall we are, the two brain pathways - POMC and AgRP - that regulate why some of us store more fat than others despite ingesting fewer calories, and the most recent effective weight loss medication weapons added to the obesity-fighting arsenal.
Ask a Doctor - What Your Doctor Wants You to Know with Dr. Virgie
In this information-packed episode, award-winning obesity medicine specialist Dr. Fatima Cody Stanford discusses new research and destroys old myths about the diseases of overweight and obesity. Dr. Stanford explains science that shows our DNA determines how much we weigh more than how tall we are, the two brain pathways - POMC and AgRP - that regulate why some of us store more fat than others despite ingesting fewer calories, and the most recent effective weight loss medication weapons added to the obesity-fighting arsenal.
Hola, soy Marco Ramón García, Otro Millennial Católico, ¿quieres saber de qué se trata este podcast? Escucha mi trailer.
References HORMONES 2013, 12(2):172-191 Proc Natl Acad Sci U S A . 2002 Dec 24;99(26):17155-60 Eur J Endocrinol. 2017 176(5): R235–R246. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
Today in the Improvement Warrior podcast Episode 13 we will discuss: Why you need to put your genitals Sunscreen sucks. Sun cosmetics episode and webinar Electrons and why they are so important. What are the cytochromes in our mitochondria Why O2 is more important than water and food. Why you shouldn't listen to people POMC, dopamine, melatonin Why dopamine is vital and what is the best way to raise it. Why is Edison in the history book and Tesla is not. Why you should never exercise wearing a mask Why being Fit doesn't make you healthy. Why losing weight doesn't equate to health To support the podcast please either leave a 5-star review on Itunes here, visit the links and sponsors of the show, or support us on Patreon. https://www.patreon.com/improvementwarrior?fan_landing=true Show notes and resources for this Improvement Warrior Podcast Episode is here at http://www.improvementwarriorfitness.com/IWP13 --- Support this podcast: https://anchor.fm/improvementwarriorpodcast/support
Huberman Lab Podcast Notes Key Takeaways Hormones are involved in both the desire to eat and satiety or reduction in appetiteEmulsifiers in highly processed foods limit the gut’s ability to identify what is in the food and send satiety signal to shut down hungerNeurons in the gut that sense sugar trigger the release of dopamine and encourage you to eat more sugarThe order you consume macronutrients influences blood glucose levels: carbs and fat early in meal give rise to blood glucose; eating fibrous vegetable first will blunt glucose increaseIf you struggle with blood glucose regulation: move or exercise before or directly after eating, be mindful of the order in which you consume foodsManaging blood glucose plays a critical role in managing cholesterol as wellOver the counter supplements that have been shown to decrease blood glucose: berberine, ginseng, magnesium, apple cider vinegar and acidic foods, yerba mate, chromiumRead the full notes @ podcastnotes.orgThis episode I discuss how hormones from our gut, liver, pancreas and brain control our appetite-- and the specific tools we can use to adjust those hormones in order to achieve specific goals. I explain the brain areas that control our desire to eat, and our desire to stop eating. I discuss a hormone we all can make that is regulated by UV-rays from sunlight that reduces our appetite. I also explain that when we eat controls our appetite and not the other way around (and how to leverage that fact). I describe how we are basically always eating until we reach a threshold level of fatty acids and amino acids in our gut and the factors that can alter that signaling and make us eat far more than we need. I also explain how insulin, glucose and glucagon work, why cholesterol is so key for ovary, adrenal, liver and testes function and how the ketogenic diet impacts glucose and thyroid levels. As always, I describe many tools: specific supplements, prescription compounds, specific types (and timing) of exercise to regulate hormones, specific timing and types of eating, ways to reduce sugar cravings by triggering release of the hormone CCK, and more. Note: A future episode will cover Thyroid hormone. Also, I mis-spoke when explaining POMC neurons. I said “P-M-O-C” but should have said “POMC”. Apologies. The name I gave for what POMC is, however, was correct: "proopiomelanocortin". Thank you to our sponsors: InsideTracker - http://insidetracker.com/huberman Athletic Greens - http://athleticgreens.com/huberman Munk Pack - http://munkpack.com - Code: huberman Our Patreon page: https://www.patreon.com/andrewhuberman Supplements from Thorne: http://www.thorne.com/u/huberman Social: Instagram - https://www.instagram.com/hubermanlab Twitter - https://twitter.com/hubermanlab Links: Dr. Lustig’s Lecture - https://www.youtube.com/watch?v=nxyxcTZccsE Paper In Cell Metabolism On Processed Food Effects - https://doi.org/10.1016/j.cmet.2019.05.008 Timestamps: 00:00:00 Introduction 00:06:59 Hunger: Neural & Hormonal Control 00:08:32 Chewing & Hunger 00:11:05 Siamese Rats Reveal the Importance of Hormones In Hunger 00:13:08 Neurons That Powerfully Control Hunger by Releasing Specific Hormones 00:16:28 Anorexia & Extreme Overeating 00:16:57 Why Sunlight Suppresses Hunger: a-Melanocyte Stimulating Hormone (a -MSH) 00:20:03 Blue-blockers, Injecting a-MSH: Instant Tan & Priapism 00:22:30 Ghrelin: A Hormone That Determines When You Get Hungry, & That You Can Control 00:24:40 Meal Timing Determines Hunger, Not the Other Way Around 00:27:20 Satchin Panda, Circadian Eating & Intermittent(ish) Fasting 00:29:35 How To Rationally Adjust Meal Schedules: The 45min Per Day Rule 00:33:02 CCK (Cholecystokinin): A Hormone In Your Gut That Says “No Mas!” 00:34:55 Eating For Amino Acids, Fatty Acids & Sugar 00:39:05 L-Glutamine: Stimulates the Immune System & Reduces Sugar Cravings 00:43:42 Things To Avoid: Emulsifiers; Alter Gut Mucosa & Nutrient Sensing 00:49:32 “A Calorie Is NOT A Calorie” After All 00:52:36 Insulin & Glucose: Hyperglycemia, Euglycemia, & Hypogylcemia 00:56:12 The Order Your Eat Foods Matters: Managing Your Blood Glucose & Glucagon 01:02:40 Movement, Exercise & GLUT-4 01:04:50 Why Sugar Stimulates Your Appetite 01:05:40 Keeping Blood Sugar Stable With Specific Exercises, The Power Of Insulin Sensitivity 01:07:55 High-Intensity Exercise, Glycogen & Metabolism 01:10:28 Cholesterol, HDL, LDL & Glucose Management: Ovaries, Testes, Liver, Adrenals 01:15:00 Prescription Compounds That Reduce Blood Glucose: Metformin 01:16:45 Berberine: A Potent Glucose Buffer That Also Adjusts Cholesterol Levels, Canker Sores 01:22:05 Chromium, L-Carnitine, Ginseng, Caffeine, Magnesium, Stevia, Vitamin B3, & Zinc 01:24:34 Acids: Vinegar, Lemons & Limes & False Alkalinity 01:26:40 Ketogenic Diets (In Brief): Effects On Blood Glucose, Thyroid Hormones 01:28:10 Diabetes, Filtering Blood, Sweet Urine 01:31:08 The Power of GLP-1 & Yerba Mate For Controlling Appetite, Electrolytes 01:35:19 Summary & Notes About Thyroid, Estrogen, Testosterone 01:37:20 Zero Cost & Sponsor-Based Ways To Support The Huberman Lab Podcast Please note that The Huberman Lab Podcast is distinct from Dr. Huberman's teaching and research roles at Stanford University School of Medicine. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Huberman Lab Podcast, its employees, guests and affiliates assume no liability for the application of the information discussed. [Title Card Photo Credit: Mike Blabac https://www.blabacphoto.com/]
Huberman Lab Podcast Notes Key Takeaways Hormones are involved in both the desire to eat and satiety or reduction in appetiteEmulsifiers in highly processed foods limit the gut’s ability to identify what is in the food and send satiety signal to shut down hungerNeurons in the gut that sense sugar trigger the release of dopamine and encourage you to eat more sugarThe order you consume macronutrients influences blood glucose levels: carbs and fat early in meal give rise to blood glucose; eating fibrous vegetable first will blunt glucose increaseIf you struggle with blood glucose regulation: move or exercise before or directly after eating, be mindful of the order in which you consume foodsManaging blood glucose plays a critical role in managing cholesterol as wellOver the counter supplements that have been shown to decrease blood glucose: berberine, ginseng, magnesium, apple cider vinegar and acidic foods, yerba mate, chromiumRead the full notes @ podcastnotes.orgThis episode I discuss how hormones from our gut, liver, pancreas and brain control our appetite-- and the specific tools we can use to adjust those hormones in order to achieve specific goals. I explain the brain areas that control our desire to eat, and our desire to stop eating. I discuss a hormone we all can make that is regulated by UV-rays from sunlight that reduces our appetite. I also explain that when we eat controls our appetite and not the other way around (and how to leverage that fact). I describe how we are basically always eating until we reach a threshold level of fatty acids and amino acids in our gut and the factors that can alter that signaling and make us eat far more than we need. I also explain how insulin, glucose and glucagon work, why cholesterol is so key for ovary, adrenal, liver and testes function and how the ketogenic diet impacts glucose and thyroid levels. As always, I describe many tools: specific supplements, prescription compounds, specific types (and timing) of exercise to regulate hormones, specific timing and types of eating, ways to reduce sugar cravings by triggering release of the hormone CCK, and more. Note: A future episode will cover Thyroid hormone. Also, I mis-spoke when explaining POMC neurons. I said “P-M-O-C” but should have said “POMC”. Apologies. The name I gave for what POMC is, however, was correct: "proopiomelanocortin". Thank you to our sponsors: InsideTracker - http://insidetracker.com/huberman Athletic Greens - http://athleticgreens.com/huberman Munk Pack - http://munkpack.com - Code: huberman Our Patreon page: https://www.patreon.com/andrewhuberman Supplements from Thorne: http://www.thorne.com/u/huberman Social: Instagram - https://www.instagram.com/hubermanlab Twitter - https://twitter.com/hubermanlab Links: Dr. Lustig’s Lecture - https://www.youtube.com/watch?v=nxyxcTZccsE Paper In Cell Metabolism On Processed Food Effects - https://doi.org/10.1016/j.cmet.2019.05.008 Timestamps: 00:00:00 Introduction 00:06:59 Hunger: Neural & Hormonal Control 00:08:32 Chewing & Hunger 00:11:05 Siamese Rats Reveal the Importance of Hormones In Hunger 00:13:08 Neurons That Powerfully Control Hunger by Releasing Specific Hormones 00:16:28 Anorexia & Extreme Overeating 00:16:57 Why Sunlight Suppresses Hunger: a-Melanocyte Stimulating Hormone (a -MSH) 00:20:03 Blue-blockers, Injecting a-MSH: Instant Tan & Priapism 00:22:30 Ghrelin: A Hormone That Determines When You Get Hungry, & That You Can Control 00:24:40 Meal Timing Determines Hunger, Not the Other Way Around 00:27:20 Satchin Panda, Circadian Eating & Intermittent(ish) Fasting 00:29:35 How To Rationally Adjust Meal Schedules: The 45min Per Day Rule 00:33:02 CCK (Cholecystokinin): A Hormone In Your Gut That Says “No Mas!” 00:34:55 Eating For Amino Acids, Fatty Acids & Sugar 00:39:05 L-Glutamine: Stimulates the Immune System & Reduces Sugar Cravings 00:43:42 Things To Avoid: Emulsifiers; Alter Gut Mucosa & Nutrient Sensing 00:49:32 “A Calorie Is NOT A Calorie” After All 00:52:36 Insulin & Glucose: Hyperglycemia, Euglycemia, & Hypogylcemia 00:56:12 The Order Your Eat Foods Matters: Managing Your Blood Glucose & Glucagon 01:02:40 Movement, Exercise & GLUT-4 01:04:50 Why Sugar Stimulates Your Appetite 01:05:40 Keeping Blood Sugar Stable With Specific Exercises, The Power Of Insulin Sensitivity 01:07:55 High-Intensity Exercise, Glycogen & Metabolism 01:10:28 Cholesterol, HDL, LDL & Glucose Management: Ovaries, Testes, Liver, Adrenals 01:15:00 Prescription Compounds That Reduce Blood Glucose: Metformin 01:16:45 Berberine: A Potent Glucose Buffer That Also Adjusts Cholesterol Levels, Canker Sores 01:22:05 Chromium, L-Carnitine, Ginseng, Caffeine, Magnesium, Stevia, Vitamin B3, & Zinc 01:24:34 Acids: Vinegar, Lemons & Limes & False Alkalinity 01:26:40 Ketogenic Diets (In Brief): Effects On Blood Glucose, Thyroid Hormones 01:28:10 Diabetes, Filtering Blood, Sweet Urine 01:31:08 The Power of GLP-1 & Yerba Mate For Controlling Appetite, Electrolytes 01:35:19 Summary & Notes About Thyroid, Estrogen, Testosterone 01:37:20 Zero Cost & Sponsor-Based Ways To Support The Huberman Lab Podcast Please note that The Huberman Lab Podcast is distinct from Dr. Huberman's teaching and research roles at Stanford University School of Medicine. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Huberman Lab Podcast, its employees, guests and affiliates assume no liability for the application of the information discussed. [Title Card Photo Credit: Mike Blabac https://www.blabacphoto.com/]
This episode I discuss how hormones from our gut, liver, pancreas and brain control our appetite-- and the specific tools we can use to adjust those hormones in order to achieve specific goals. I explain the brain areas that control our desire to eat, and our desire to stop eating. I discuss a hormone we all can make that is regulated by UV-rays from sunlight that reduces our appetite. I also explain that when we eat controls our appetite and not the other way around (and how to leverage that fact). I describe how we are basically always eating until we reach a threshold level of fatty acids and amino acids in our gut and the factors that can alter that signaling and make us eat far more than we need. I also explain how insulin, glucose and glucagon work, why cholesterol is so key for ovary, adrenal, liver and testes function and how the ketogenic diet impacts glucose and thyroid levels. As always, I describe many tools: specific supplements, prescription compounds, specific types (and timing) of exercise to regulate hormones, specific timing and types of eating, ways to reduce sugar cravings by triggering release of the hormone CCK, and more. Note: A future episode will cover Thyroid hormone. Also, I mis-spoke when explaining POMC neurons. I said “P-M-O-C” but should have said “POMC”. Apologies. The name I gave for what POMC is, however, was correct: "proopiomelanocortin". Thank you to our sponsors: InsideTracker - http://insidetracker.com/huberman Athletic Greens - http://athleticgreens.com/huberman Munk Pack - http://munkpack.com - Code: huberman Our Patreon page: https://www.patreon.com/andrewhuberman Supplements from Thorne: http://www.thorne.com/u/huberman Social: Instagram - https://www.instagram.com/hubermanlab Twitter - https://twitter.com/hubermanlab Links: Dr. Lustig’s Lecture - https://www.youtube.com/watch?v=nxyxcTZccsE Paper In Cell Metabolism On Processed Food Effects - https://doi.org/10.1016/j.cmet.2019.05.008 Timestamps: 00:00:00 Introduction 00:06:59 Hunger: Neural & Hormonal Control 00:08:32 Chewing & Hunger 00:11:05 Siamese Rats Reveal the Importance of Hormones In Hunger 00:13:08 Neurons That Powerfully Control Hunger by Releasing Specific Hormones 00:16:28 Anorexia & Extreme Overeating 00:16:57 Why Sunlight Suppresses Hunger: a-Melanocyte Stimulating Hormone (a -MSH) 00:20:03 Blue-blockers, Injecting a-MSH: Instant Tan & Priapism 00:22:30 Ghrelin: A Hormone That Determines When You Get Hungry, & That You Can Control 00:24:40 Meal Timing Determines Hunger, Not the Other Way Around 00:27:20 Satchin Panda, Circadian Eating & Intermittent(ish) Fasting 00:29:35 How To Rationally Adjust Meal Schedules: The 45min Per Day Rule 00:33:02 CCK (Cholecystokinin): A Hormone In Your Gut That Says “No Mas!” 00:34:55 Eating For Amino Acids, Fatty Acids & Sugar 00:39:05 L-Glutamine: Stimulates the Immune System & Reduces Sugar Cravings 00:43:42 Things To Avoid: Emulsifiers; Alter Gut Mucosa & Nutrient Sensing 00:49:32 “A Calorie Is NOT A Calorie” After All 00:52:36 Insulin & Glucose: Hyperglycemia, Euglycemia, & Hypogylcemia 00:56:12 The Order Your Eat Foods Matters: Managing Your Blood Glucose & Glucagon 01:02:40 Movement, Exercise & GLUT-4 01:04:50 Why Sugar Stimulates Your Appetite 01:05:40 Keeping Blood Sugar Stable With Specific Exercises, The Power Of Insulin Sensitivity 01:07:55 High-Intensity Exercise, Glycogen & Metabolism 01:10:28 Cholesterol, HDL, LDL & Glucose Management: Ovaries, Testes, Liver, Adrenals 01:15:00 Prescription Compounds That Reduce Blood Glucose: Metformin 01:16:45 Berberine: A Potent Glucose Buffer That Also Adjusts Cholesterol Levels, Canker Sores 01:22:05 Chromium, L-Carnitine, Ginseng, Caffeine, Magnesium, Stevia, Vitamin B3, & Zinc 01:24:34 Acids: Vinegar, Lemons & Limes & False Alkalinity 01:26:40 Ketogenic Diets (In Brief): Effects On Blood Glucose, Thyroid Hormones 01:28:10 Diabetes, Filtering Blood, Sweet Urine 01:31:08 The Power of GLP-1 & Yerba Mate For Controlling Appetite, Electrolytes 01:35:19 Summary & Notes About Thyroid, Estrogen, Testosterone 01:37:20 Zero Cost & Sponsor-Based Ways To Support The Huberman Lab Podcast Please note that The Huberman Lab Podcast is distinct from Dr. Huberman's teaching and research roles at Stanford University School of Medicine. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Huberman Lab Podcast, its employees, guests and affiliates assume no liability for the application of the information discussed. [Title Card Photo Credit: Mike Blabac https://www.blabacphoto.com/]
Proceedings of The Nutrition Society.2012 71(4):521-33 Autophagy. 2009 May; 5(4): 558–560 Molecular and Cellular Endocrinology Volume 472, 5 September 2018, Pages 40-49 Int J Mol Sci. 2020 Nov; 21(21): 8220. --- Send in a voice message: https://anchor.fm/dr-daniel-j-guerra/message Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
La regulación de la ingesta de comida y las sensaciones de hambre o saciedad dependen de la integración de señales metabólicas en una estructura del cerebro llamada hipotálamo. El funcionamiento de este circuito depende del estado energético de un animal, pero recientemente hemos aprendido que a veces no es necesario comer para que el cerebro apague la señal que nos induce a buscar comida. En el capítulo de hoy hablaremos de comida y cómo el cerebro regula la ingesta de calorías, escarbaremos en la glotonería de los perros labradores y les contaré la historia de la persona más hambrienta de la historia *** La Ciencia Pop es auspiciado por Más Audio, donde cuentan con la tecnología más avanzada y los más cómodos y modernos audífonos de origen alemán. Con los mejores precios del mercado, tecnología de punta y un servicio de primer nivel, en Más Audio te pueden ayudar a ti o un familiar a volver a oír los sonidos que ya no escuchas. Para más información, visita la página www.masaudio.cl o escribe al correo quiero@masaudio.cl. También puedes visitar sus páginas en Facebook o su tienda online en tienda.masaudio.cl y mencionando “La Ciencia Pop”, te darán un 5% de descuento en la compra de audífonos. No te lo pierdas ***Support the show (https://www.patreon.com/LaCienciaPop)
Rhythm Pharmaceuticals gets FDA approval for Setmelanotide (IMCIVREE) for Chronic Weight Management in Patients with Obesity due to POMC, PCSK1 or LEPR Deficiency (Age 6 and older). The management team also gave pricing information, indicating $330/mg and blended pricing estimate of $290-300K/patient/year. The stock rose about 21% on this news and I discuss the implications and future catalysts. Anavex's ANAVEX2-73 (Blarcamesine) is being investigated for Alzheimer's Disease, Parkinson's Disease and Rett Syndrome. I go through the latest data and catalysts that are approaching for the company. I also touch on $HEPA's latest press releases. If you want to help out the show (or join the discord), take a look at my patreon: https://www.patreon.com/breakingbiotech Follow me on twitter @matthewlepoire Send me an email matthewlepoire@gmail.com www.breakingbiotech.com #breakingbiotech Disclaimer: All opinions expressed by Matt in this podcast are solely his opinions. You should not treat any opinion expressed by Matt in this podcast as a specific inducement to make a particular investment or follow a particular strategy, but only as an expression of his opinion. Matt's opinions are based upon information he considers reliable, but Matt cannot warrant its completeness or accuracy, and it should not be relied upon as such. Matt is not under any obligation to update or correct any information provided in this podcast. Past performance is not indicative of future results. Matt does not guarantee any specific outcome or profit. You should be aware of the real risk of loss in following any strategy or investment discussed in this podcast. #biotech
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.07.21.214296v1?rss=1 Authors: Perissinotti, P., Martinez-Hernandez, E., Piedras-Renteria, E. S. Abstract: Leptin regulates hypothalamic POMC+ (pro-opiomelanocortin) neurons by inducing TRPC (Transient Receptor Potential Cation) channel-mediate membrane depolarization. Here we assessed the role of T-type channels on POMC neuron excitability and leptin-induced depolarization in vitro. We demonstrate T-type currents are indispensable for both processes, as treatment with NNC-55-0396 prevented the membrane depolarization and rheobase changes induced by leptin in cultured mouse POMC neurons. Furthermore, we demonstrate TRPC1/C5 channels and CaV3.1 and CaV3.2 channels co-exist in complex. The functional relevance of this complex was corroborated using intracellular Ca2+ chelators; intracellular BAPTA (but not EGTA) application was sufficient to preclude POMC neuron excitability by preventing leptin-induced calcium influx through TRPC channels and T-type channel function. We conclude T-type channels are integral in POMC neuron excitability. Leptin activation of TRPC channels existing in a macromolecular complex with T-type channels recruits the latter by locally-induced membrane depolarization, further depolarizing POMC neurons, triggering action potentials and excitability. Copy rights belong to original authors. Visit the link for more info
Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.06.25.172379v1?rss=1 Authors: Moura-Assis, A., de Lima-Junior, J. C., Nogueira, P. A., Simabuco, F. M., Gaspar, J. M., Junior, J. D., Velloso, L. A. Abstract: In a public dataset of transcripts differentially expressed in selected neuronal subpopulations of the arcuate nucleus, we identified TLR4-interactor with leucine-rich repeats (Tril) as a potential candidate for mediating the harmful effects of a high-fat diet in proopiomelanocortin (POMC) neurons. The non-cell-specific inhibition of Tril in the arcuate nucleus resulted in reduced hypothalamic inflammation, protection against diet-induced obesity associated with increased whole-body energy expenditure and increased systemic glucose tolerance. The inhibition of Tril, specifically in POMC neurons, resulted in a trend for protection against diet-induced obesity, increased energy expenditure and increased hypothalamic sensitivity to leptin. Thus, Tril emerges as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental diet-induced obesity. Copy rights belong to original authors. Visit the link for more info
En una más de las reflexiones escritas de Pensando: El feminismo, como muchas ideologías, en realidad no se trata de "movimientos" o "expresiones" de la sociedad, sino de un sistema bastante bien organizado que no se diferencia mucho de una religión.
Te cuento qué es la Misa Tridentina y cómo fue mi primera experiencia asistiendo a ella. Créeme, no te vas a arrepentir de asistir.
Dr Guerra opens up the refereed published scientific literature to provide verified evidence associated with the arcuate nucleus of the hypothalamic arc leading to hormonal control over nutrition and the immune system. Published 28 April 2020 --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
The 3 Men listen to your questions and comments, share another expert opinion about this case, learn about a great organization called Parents of Murdered Children, and honor the life of Elisa Gomez.This episode sponsored by:http://www.betterhelp.com/3MenLearn more about Parents of Murdered Children at www.POMC.orgLearn more about us at http://www.3menandamystery.comLearn more about your ad choices. Visit megaphone.fm/adchoices
There is a room in a home in Pennsylvania where purple dinosaur Barney stuffed animals wait silently for a little girl who will never come. The collection is in memory of the petite toddler who loved Barney, loved life and was loved in return by her mother, aunt, grandparents, and others. But the evening of March 12, 1994, tiny Lisa Marie McGhee was brutally murdered by her mother's live-in boyfriend, William Everhart who towered over her at 6'6" tall with a temper to match. No amount of time, explanation, tears or sharing of memories will bring peace to the grieving family. Lisa should have been age 26 at the time I spoke with her aunt, cousin and a younger sister (that she never met). Lisa's family reiterates the dreadful events that led to her death and the unspeakable loss that followed. They explain the actions their extended family took to heal and honor their smallest relative whose life was taken before she even started school. Lisa will remain an innocent 2 1/2-year-old, with an infectious smile, sprout of straight blond hair and love of purple dinosaurs.
It’s February WOW! the year is moving , this episode is a introduction to POMC for 2020 wishing you all love and hope you keep coming back for some amazing content !
Dr Dan Guerra pursues how Leptin and POMC regulate neuroendocrine and neuro-appetitive behaviours that link obesity and associated metabolic and life-style disease with the dysregulation of energy homeostasis --- Support this podcast: https://anchor.fm/dr-daniel-j-guerra/support
00:51 | Cerebellum Functions 06:28 | Sponsored by HAPS 06:52 | Liver Responds to Food Stimuli 09:06 | Sponsored by AAA 09:26 | Exercise, Diet, Metabolism, & Body Weight 17:29 | Sponsored by HAPI Online Graduate Program 17:58 | Featured: Language of Muscles: A Strategy for Learning If you cannot see or activate the audio player click here. Questions & Feedback: 1-833-LION-DEN (1-833-546-6336) Follow The A&P Professor on Twitter, Facebook, Blogger, Nuzzel, Tumblr, or Instagram! If you've got a big gut and you start doing sit-ups, you are going to get bigger because you build up the muscle. You've got to get rid of that fat! How do you get rid of fat? By changing your diet. (Jack LaLanne) 1 | Cerebellum Functions 5.5 minutes The cerebellum is well known for planning and coordination of motor programs. But there's more to it! The Cerebellum Is Your "Little Brain"—and It Does Some Pretty Big Things (article from Scientific American) my-ap.us/2UrcmCg Making Moves and Memories: Are They Connected? (summary article) my-ap.us/2UsHscJ A cortico-cerebellar loop for motor planning (research article) my-ap.us/2UsHtNP Functional topography in the human cerebellum: A meta-analysis of neuroimaging studies (research article) my-ap.us/2UB3mKM Cerebellar modulation of the reward circuitry and social behavior (research article) my-ap.us/2UB3nyk Short latency cerebellar modulation of the basal ganglia (research article) my-ap.us/2UsXJP3 The cerebellum gets social (commentary in Science) my-ap.us/2UsXKT7 The Role of the Cerebellum in Cognitive and Affective Processes (online reference module) my-ap.us/2UsCVab The Somatic Nervous System (online reference module) my-ap.us/2UwiitO 2 | Sponsored by HAPS 0.5 minute The Human Anatomy & Physiology Society (HAPS) is a sponsor of this podcast. Did you know there's a one-day regional HAPS conference in March? Check it out. You can help appreciate their support by clicking the link below and checking out the many resources and benefits found there. Anatomy & Physiology Society theAPprofessor.org/haps 3 | Liver Anticipates Food 2 minutes We know that digestive organs respond to anticipation of food—as if food really is going to be ingested and swallowed. New research suggests that the sight of a donut (for example) can get our hepatic cells to start revving up for the storage and processing of nutrients during the absorptive state. POMC is short for proopiomelanocortin The role of proopiomelanocortin (POMC) neurones in feeding behaviour (review article) my-ap.us/2UqukVn Just the Sight of Food Gets the Liver Ready for Action (summary article) my-ap.us/2UvyjAi Food Perception Primes Hepatic ER Homeostasis via Melanocortin-Dependent Control of mTOR Activation (research article) my-ap.us/2UtU7ML 4 | Sponsored by AAA 0.5 minutes The searchable transcript for this episode, as well as the captioned audiogram of this episode, are sponsored by The American Association of Anatomists (AAA) at anatomy.org. Their big meeting is in April at the Experimental Biology (EB) meeting in Orlando FL. Check it out! Searchable transcript Captioned audiogram 5 | What Do We Really Know About Exercise, Diet, Metabolism, & Body Weight? 8 minutes The science of exercise, diet, metabolism, and body weight—and what is healthy and what is not—is far from being worked out. Sometimes, the simplest principles that we believe to be true, aren't really. A of research seems to conflict, which means we have much more work to do, eh? If you are fan of stories without a satisfying ending and conflicting subplots, follow the [whole grain] bread crumbs here: Why doing more exercise won't help you burn more calories (summary article) my-ap.us/2UvbkFv No sweat: The smart guide to exercise (summary article) my-ap.us/2UvLlxw Hunter-Gatherer Energetics and Human Obesity (research article) my-ap.us/2UxlGog Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans. (research article) my-ap.us/2UuYAi3 Is there spontaneous energy expenditure compensation in response to intensive exercise in obese youth? (research article) my-ap.us/2UsT53j The workout pill: Why exercise is the best medicine (summary article points out exercise benefits other than weight control) my-ap.us/2UtGtcf Persistent metabolic adaptation 6 years after “The Biggest Loser” competition (research article) my-ap.us/2UAvTR3 Do skinny people have faster metabolisms? Not really (summary article) my-ap.us/2Uu0WxR Non-exercise activity thermogenesis (NEAT). (descriptive article) my-ap.us/2UvL91w Slim people have a genetic advantage when it comes to maintaining their weight (summary article) my-ap.us/2UvPxxc Genetic architecture of human thinness compared to severe obesity (research article) my-ap.us/2UpkWS2 Top 10 Reasons Why The BMI Is Bogus (summary article) my-ap.us/2UAwdzf The Health Risk of Obesity—Better Metrics Imperative (perspective article in Science) my-ap.us/2UvLkKe Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity (research article) my-ap.us/2UpNATe Is the doughnut diet too good to be true? (umm...) my-ap.us/2UtRyKz 6 | Sponsored by HAPI Online Graduate Program 0.5 minutes The Master of Science in Human Anatomy & Physiology Instruction—the MS-HAPI—is graduate program for A&P teachers. A combination of science courses (enough to qualify you to teach at the college level) and courses in instructional practice, this program helps you power up your teaching. Kevin Patton is a faculty member in this program. Check it out! nycc.edu/hapi 7 | Featured: Language of Muscles: A Strategy for Learning 17 minutes Learning the major muscles of the body can be intimidating for students. But if they understand from the start that those unusual names are more than a tongue-twisting combination of syllables—that they actually have meaning—they can use muscle names as mnemonic aids to learning. Muscle names can help students remember muscles by reminding them of the muscle's location, function, shape, size, and/or other characteristics. Muscle Names Have Meaning (Lion Den summary for students, with additional links/video, link to handouts) lionden.com/tips-lab-anatomy-muscle-names.htm Download link for handouts Muscle Names List MS Word (.docx) version Muscle Names List PDF (portable document file) version Translating muscle names (article from The A&P Student blog) my-ap.us/2UveAkd Nine Super Strategies for Teaching the Skeleton | Episode 10 (previous episode in which I outline a similar strategy for learning bones) If the hyperlinks here are not active, go to TAPPradio.org to find the episode page. More details at the episode page. Transcript available at the script page. Listen to any episode on your Alexa device. Need help accessing resources locked behind a paywall? Check out this advice from Episode 32 to get what you need! https://youtu.be/JU_l76JGwVw?t=440 Sponsors Transcript and captions for this episode are supported by the American Association of Anatomists. anatomy.org The Human Anatomy & Physiology Society also provides marketing support for this podcast. theAPprofessor.org/haps Distribution of this episode is supported by NYCC's online graduate program in Human Anatomy & Physiology Instruction (HAPI) nycc.edu/hapi Amazon and TextExpander referrals help defray podcasting expenses. (Clicking on sponsor links helps let them know you appreciate their support of this podcast!) Follow The A&P Professor on Twitter, Facebook, Blogger, Nuzzel, Tumblr, or Instagram!
Kriben Govender (Honours Degree in Food Science & Technology) and Jame Shadrach (Honours Degree in Psychology) have a mind expanding discussion with neurosurgeon Dr Jack Kruse on how light may sculpt the microbiome and the implications for optimising your overall health today. Bio: Dr. Jack Kruse is a respected neurosurgeon and CEO of Optimized Life, a health and wellness company dedicated to helping patients avoid the healthcare burdens we typically encounter as we age. He is currently in private practice in the Gulf South. As a neurosurgeon, Dr. Kruse’s research has been published in respected dental and medical journals. His popular blog, www.JackKruse.com, gets over 250,000 unique worldwide visitors per month from countries like Australia, Germany, Russia, and Zambia (Africa). Topics discussed: Jack’s health crisis The book that inspired Jack’s journey https://www.amazon.com/Monk-Who-Sold-His-Ferrari/dp/0062515675 Obesity linked to blue light, sunlight and non native electromagnetic fields Unlearning to relearn POMC https://en.wikipedia.org/wiki/Proopiomelanocortin POMC and morning sunlight (sunrise to 10am) The Sphinx Depression and Dopamine Serotonin, Melatonin and the Gut Brain Axis Tryptophan, melatonin and Cytochrome C Melatonin and mitochondrial autophagy and apoptosis Artificial Light at Night (ALAN) impact on Gut and Brain Light sculpts the microbiome Surfaces exposed to light: eye, skin and gut Leptin stimulus What is Melanopsin? Bacteria and light Fritz Popp and Biophotons- extreme low frequency ultra violet light https://en.wikipedia.org/wiki/Fritz-Albert_Popp Microbiome as a light intermediary Jeff Leech, Hazda Study https://youtu.be/tjLW_DaQ9qI The impact of human migration on the microbiome Bacteria and UV light NADH, Niacin and tryptophan The carbohydrate photon and Electron link via the Einstein’s photo electric effect Eye, skin and gut yolking Gut metabolite Methane: the hydrogen store Hydrogen Sulphide: gasotransmitter https://en.wikipedia.org/wiki/Gaseous_signaling_molecules#Sulfur_dioxide Nitric Oxide and electron chain transport Red light and ATPase Calorie restriction and sunlight Sulfation: Mission microbiome Sulfation of blood and cholesterol Red light and the gut microbiome Methionine Cycle and heavy metals Riboflavin (B2) and Sulfation Blue light and the microbiome Sculpting the microbiome with sunlight The Epi Paleo Rx https://www.amazon.com/Epi-paleo-Rx-Prescription-Disease-Reversal-ebook/dp/B00BIUAZUQ Diet and light Photobiomodulation Tina Kuru Jeff Leech’s new study Jack’s No 1 Gut health recommendation: https://www.amazon.com/Light-shaping-life-Biophotons-medicine/dp/9081884328 Brought to you by: Nourishme Organics- Gut Health Super Store- Shine from the Inside Shop Gut Health and Fermentation- 10% off using code: jack https://www.nourishmeorganics.com.au/collections/beginner-recommendations-start-here Allele Microbiome- Gut Microbiome and Deuterium Testing Microbiome Stool testing (10% off Gut Explorer Pro Kit using code: gutlove) https://www.allele.com.au/collections/frontpage/products/gut-microbiome-analysis Deuterium Testing (10% off Deuterium Explorer Kit using code: deuterium) https://www.allele.com.au/collections/frontpage/products/deuterium-explorer Connect with Dr Jack Kruse Website- https://jackkruse.com/ Connect with Kriben Govender: Facebook- https://www.facebook.com/kribengee/ Instagram- https://www.instagram.com/kribengovender/ Youtube- https://www.youtube.com/c/Nourishmeorganics?sub_confirmation=1 Gut Health Gurus Facebook Group: https://www.facebook.com/groups/nourishmeorganics/ Mito Wellness Support Facebook Group: https://www.facebook.com/groups/347845406055631/ Download links If you enjoyed this episode and would like to show your support: 1) Please subscribe on Itunes and leave a positive review Instructions: - Click this link https://itunes.apple.com/au/podcast/gut-health-gurus-podcast/id1433882512?mt=2 - Click "View in Itunes" button on the left hand side - This will open Itunes app - Click "Subscribe" button - Click on "Ratings and Reviews" tab - Click on "Write a Review" button Non Itunes user’s can leave a Google Review here: http://bit.ly/nourishmeorganics 2) Subscribe, like and leave a positive comment on Youtube https://www.youtube.com/c/Nourishmeorganics?sub_confirmation=1 3) Share your favourite episode on Facebook, Instagram, and Stories 4) Let your friends and family know about this Podcast by email, text, messenger etc 5) Support us on Patreon for as little as $5 per month and get same day, early access to our latest podcasts (typically around 4 to 6 weeks earlier than the general public) https://www.patreon.com/nourishmeorganics Thank you so much for your support. It means the world to us.
Dr. Eleanor Raffen, Wellcome Trust Clinical Research Fellow, University of Cambridge.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 05/06
Epigenetic programming facilitates the adaptation of an organism to changes in the environment through lasting alterations in gene expression that underlie certain physical and behavioral phenotypes. Exposure to adverse events in early postnatal life is known to increase the risk for stress-related psychiatric disorders later on. Our previous studies showed that early-life stress (ELS) in mice caused by periodic infant-mother separation (MS) leads to increased hyperactivity of the HPA axis, reduced glucocorticoid feedback inhibition, and depressive-like behavior. Moreover, our work revealed ELS-induced hypomethylation of the arginine vasopressin (Avp) gene enhancer and pro-opiomelanocortin (Pomc) promoter. The aim of the study was to investigate whether ELS can also lead to epigenetic programming of the mouse glucocorticoid receptor (GR, Nr3c1). GR is a major feedback regulator of the hypothalamic-pituitary adrenal (HPA) stress axis and its expression is regulated by multiple promoters associated with its5’ untranslated first exons. Given the fact that the mouse GR promoter was only partly characterized, we aimed to determine its genomic structure. In addition, tissue distribution and absolute quantification of newly identified alternative first exon transcripts were analysed. Although most of the first exon transcripts were found to be widely expressed, some of them are shown to be differentially regulated by growth factor- and depolarization-induced signaling. In the present work we show also that mice with a history of maternal separation display up-regulated GR mRNA levels. This observation was confined to Crh-producing neurons in the hypothalamic paraventricular nucleus (PVN), which are principal effectors of the stress response. Moreover, elevated levels of GR are shown to be responsible for stronger induction of its downstream target genes (Fkbp5, Sgk1, and DUSP1), which suggests an enhanced transcriptional activity of the GR in ELS mice. This effect is supported by a higher occupancy of the GR at the glucocorticoid response elements (GREs), following corticosterone injection (i.p.). Finally, we report here that an enhanced level of GR expression in ELS mice is accompanied by an increased methylation of specific CpG residues at the CpG island shore region of the GR promoter. These ELS-responsive CpGs comprise a DNA binding site for the transcriptional repressor Yin Yang 1 (YY1). Given the high homology of the mouse and human GR promoter, and the conservation of the YY1 binding site, we conducted a methylation analysis of the hGR CpG island shore region in peripheral tissues and post mortem brain samples. Our findings might serve as a basis for comparing the methylation patterns in tissues from control subjects and patients with stress-related brain disorders.
Fakultät für Biologie - Digitale Hochschulschriften der LMU - Teil 04/06
Early-life stress (ELS) can lead to enduring changes in the structure and function of neural circuits and endocrine pathways, resulting in altered vulnerability thresholds for stress-related disorders such as depression and anxiety. The question addressed in this work was whether epigenetic mechanisms contribute to the long-term programming of altered hypothalamus-pituitary-adrenal axis activity in ELS (maternal separated on postnatal days 1-10) mice. Adrenocorticotropic hormone (ACTH), a key pituitary mediator of the adrenocortical response to stress, is encoded by the proopiomelanocortin (Pomc) gene. Corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) are the main upstream neural regulators of Pomc gene expression and the post-translational processing of its peptidergic products, whereas glucocorticoids, secreted by the adrenals in response to stress, exert negative feedback actions on Pomc synthesis and ACTH secretion. It was shown that Pomc mRNA level is persistently increased in ELS mice and leads to sustained hypersecretion of glucocorticoids. Interestingly, ELS causes a reduction in DNA methylation at a critical regulatory region of the Pomc gene; this occurs with some delay after onset of the stress and persists for up to 1 year. A series of experiments (including reporter-, EMSA-, IHC- and ChIP-assays) supported the concept that the adverse early-life event induces changes in Pomc gene methylation and results in persistently upregulated expression of the Pomc gene. Interestingly, stress-induced changes in DNA-methylation were found to be more pronounced in males than in females, raising the possibility that epigenetic encoding occurs in a sex-specific manner; this may help to explain sex differences in susceptibility to stress-related disorders. Collectively, the results of this study indicate that epigenetic mechanisms can serve to translate environmental cues into stable changes (“cellular memory”) in gene expression in post-mitotic tissues, without the need for alterations in the genetic code.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 04/19
Diese Arbeit konnte Oncostatin M als Modulator der Hypothalamus-Hypophysen-Nebennierenrinden-Achse näher charakterisieren. Es konnte gezeigt werden, dass Oncostatin M an hypophysärem Gewebe über den gp130/LIFR-Komplex zur Aktivierung der Jak-STAT-Kaskade mit folgender STAT-abhängiger POMC- und STAT3-Expression und schließlich zur ACTH-Ausschüttung führt. Da über den gp130/OSMR-Rezeptorkomplex keine Jak-STAT-Aktivierung mit konsekutiver POMC- und STAT3-Expression und ACTH-Sekretion nachgewiesen werden konnte, wird postuliert, dass Oncostatin M an der Modulation der corticotrophen Funktion über den gp130/LIFR-Komplex, nicht jedoch über den gp130/OSMR-Komplex beteiligt ist. Auf adrenocorticaler Zellebene konnte erstmals ein direkter stimulierender Effekt von Oncostatin M auf die Steroidsekretion gezeigt werden. Murines OSM führt über den gp130/OSMR-Rezeptor-Komplex, humanes OSM und murines LIF zur Aktivierung der Jak-STAT-Kaskade und zur Steroidausschüttung durch murine Y-1 Zellen. Damit konnte Onostatin M als potenter Modulator der adrenocorticalen Zellfunktion charakterisiert werden. Erstmals wurde hier die Induktion von Apoptose durch OSM an adrenocorticalen Tumorzellen beschrieben. Es bleibt zu zeigen, dass der an der murinen Zelllinie Y-1 nachgewiesen Effekt auch auf humane Tumorzellen übertragbar ist. Ein zellspezifischer apoptotischer Effekt von OSM auf adrenocorticale Tumorzellen könnte ein potentieller wertvoller Mechanismus zur Entwicklung einer spezifischen Therapie des hochmalignen Nebennierenrindencarcinoms darstellen.
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 02/19
Thu, 27 May 2004 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/2245/ https://edoc.ub.uni-muenchen.de/2
Medizinische Fakultät - Digitale Hochschulschriften der LMU - Teil 02/19
This work investigates for the first time the expression and the role of Sonic hedgehog signaling pathway in adult pituitary and in pituitary tumors. Shh is a signaling protein, important in regulating patterning and proliferation in the embryo and the adult. It has a crucial role in pituitary development and Shh deficient mice do not even have a rudimentary Rathke's pouch (the development structure that gives rise to anterior pituitary). This study reveals the presence of an active Shh pathway in the post-developmental pituitary gland, with major impacts on hormone secretion and cell proliferation. After embryonic development, Shh continues to be expressed in the normal adult pituitary, being mainly co-localized in corticotrophs. These cells express also the receptor Ptc2 and the Shh induced transcription factor Gli1, being so Shh-producing and Shh-responsive cells. Shh acts in an autocrine way inside corticotrophs, inducing a major stimulation of ACTH secretion in the normal rat pituitary and in the AtT-20 cell line. The Shh induced ACTH secretion effect is synergistic with CRH. Shh stimulation increases CRH-R1 levels, up-regulating so the response of corticotrophs to CRH. At the same time, Gli1 is not only activated by Shh, but also by CRH and PKA. Gli1 itself activates POMC-transcription and acts in parallel upstream to CREB and AP-1. A major increase in Shh protein levels is seen as a result of CRH stimulation. All these results put in evidence a multiple cross-talk between these two important pathways acting at different levels to insure the final ACTH stimulation. Other types of hormone-secreting adenohypophysial cells possess one of Shh receptors (Ptc1 or Ptc2) and the transcription factor Gli1, so they have an active Shh pathway. Shh produced in the corticotrophs is a signaling protein, so it diffuses and acts also in distance. Shh increases GH secretion from the rat pituitary somatotrophs and from the GH3 cell line, while the effect on Prolactin is not statistically significant. The Sonic hedgehog pathway is downregulated in pituitary adenomas. Screening of 55 pituitary tumors reveals that they have a significantly reduced expression of Shh and Gli1. Although Shh in the normal pituitary is secreted by corticotroph cells, all the Cushing tumors screened had no Shh expression at all. Cell culture experiments performed in the AtT-20 corticotroph cell line in vitro show that Shh reduces cell proliferation by 50% and this effect is partially reducible by Cyclopamine. So Shh maintains the low proliferative capacity of corticotrophs in the normal pituitary gland and its loss may be one of the factors leading to tumor progression. It is concluded that Shh is produced in the anterior pituitary gland, is a major stimulant of ACTH and GH secretion, acts synergistically with CRH, opposes corticotroph cell proliferation and is downregulated in pituitary adenomas.
Objective: This comparative in vitro study examined the effects of all known gp130 cytokines on murine corticotroph AtT-20 cell function. Methods: Cytokines were tested at equimolar concentrations from 0.078 to 10 nM. Tyrosine phosphorylation of the signal transducer and activator of transcription ( STAT) 3 and STAT1, the STAT-dependent suppressor of cytokine signaling (SOCS)-3 promoter activity, SOCS-3 gene expression, STAT-dependent POMC promoter activity and adrenocorticotropic hormone ( ACTH) secretion were determined. Results: Leukemia inhibitory factor (LIF), human oncostatin M (OSM) and cardiotrophin (CT)-1 (LIFR/gp130 ligands), as well as ciliary neurotrophic factor ( CNTF) and novel neurotrophin1/B-cell stimulating factor-3 (CNTFRalpha/LIFR/gp130 ligands) are potent stimuli of corticotroph cells in vitro. In comparison, interleukin (IL)-6 (IL-6R/gp130 ligand) and IL-11 (IL-11R/gp130 ligand) exhibited only modest direct effects on corticotrophs, while murine OSM (OSMR/gp130 ligand) showed no effect. Conclusion: (i) CNTFR complex ligands are potent stimuli of corticotroph function, comparable to LIFR complex ligands; (ii) IL-6 and IL-11 are relatively weak direct stimuli of corticotroph function; (iii) differential effects of human and murine OSM suggest that LIFR/gp130 (OSMR type I) but not OSMR/gp130 (OSMR type II) are involved in corticotroph signaling. (iv) CT-1 has the hitherto unknown ability to stimulate corticotroph function, and (v) despite redundant immuno-neuroendocrine effects of different gp130 cytokines, corticotroph cells are preferably activated through the LIFR and CNTFR complexes. Copyright (C) 2004 S. Karger AG, Basel.
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