Podcasts about mc4r

Episode Highlights With Dr. Erika GrayImportant perspective about genetics and how to use this information for the biggest advantageThe nuance when it comes to children and genes Genes do not exist in isolation and why focusing on one gene is not helpfulHow understanding genetics helped her teens (and mine)What COMT is and how this comes into play with influencing our worldviewFast COMT break down dopamine and norepinephrine faster (linked to moving around, not sitting still, etc.)How this understanding of genetics can relate directly to how we parent Yet another reason protein is so important, especially for kids and teens Genes related to serotonin and dopamine and neurotransmittersWe have 2-5 lbs of bacteria in our gut, and there is a gene called FUT2 that ties to lower levels of bifidobacteria, and this can be linked to anxiety, longevity, and moreUnderstanding choline genes and why this is a game changer for so many people, and this is critical for pregnancy and brain development Some caveat around MTHFR and why we might be overdoing our response to thisSerotonin-related genes to look at if you get your kids' genes testedWhat BDNF genes can tell youMC4R is a snacking gene, and how to understand thisBitter taste receptor genes and how these can make kids more pickyResources We MentionMy Toolbox Genomics - Use code wellnessmama for a discountKion Aminos

Summary In this episode of the "Muscles and Mindset" podcast, Ali Novitsky MD dives deep into the fascinating science of hunger. She starts by sharing her personal experience with having a big appetite and how it led her to explore the genetics of hunger. Dr. Ali explains that hunger actually has a genetic component, specifically related to the MC4R gene, which affects our satiety levels. She reveals that she has a variant in this gene, which explains her larger-than-average appetite. Moving on, Dr. Ali discusses the different hormones involved in hunger. She explores ghrelin, known as the "ghrelin gremlin," which is the hunger hormone that increases in situations of stress, sleep deprivation, and weight loss. On the other hand, she explains that leptin is the satiety hormone produced in our fat cells. Dr. Ali also highlights the concept of leptin resistance, where the brain doesn't sense enough body fat despite high levels of leptin, believed to contribute to obesity. Dr. Ali further touches on insulin, which is responsible for lowering blood glucose levels and driving nutrients into cells. She explains how high insulin responses to unopposed carbohydrates can lead to rebound hunger. Lastly, she mentions cortisol, the stress hormone, which can increase blood sugar levels and inhibit insulin release, potentially causing insulin resistance. Throughout the episode, Dr. Ali emphasizes the importance of understanding these hunger hormones and their impact on our appetite. She mentions that in the next episode, she will discuss strategies to optimize hunger and regulate appetite naturally, including dietary and exercise approaches. Dr. Ali also highlights some of the programs and services available to listeners, such as a muscle maintenance and weight loss program, a 31-day fitness program, and a six-month coaching program specifically designed for women physicians. Overall, this episode of "Muscles and Mindset" provides listeners with a better understanding of the science behind hunger and how they can work with their hunger to achieve their health and weight loss goals.   Takeaways Hunger has a genetic component, with the MC4R gene affecting satiety. There is no 'normal' appetite, and each person's appetite is unique. Hunger is a sensation, not a feeling, and can be accompanied by different emotions. Hormones such as ghrelin, leptin, insulin, and cortisol play a role in hunger regulation.   Chapters 00:00 Introduction to the Science of Hunger   01:29 Genetics of Hunger   04:43 Defining Normal Appetite   05:12 Understanding Hunger   08:02 Hormones Involved in Hunger: Ghrelin   09:30 Hormones Involved in Hunger: Leptin   10:29 Hormones Involved in Hunger: Insulin   17:19 Hormones Involved in Hunger: Cortisol   19:41 Strategies for Managing Hunger   Resources Mentioned Find Ali Novitsky MD Online Follow Dr. Ali Novitsky on Facebook | Instagram | TikTok Subscribe to Muscles & Mindset on Apple Podcasts   *** Ali Novitsky MD, this podcast, and podcast write-up are NOT providing medical advice ***

URGENT MESSAGE: Denise has generously organised a 20% discount for the first 60 people to purchase her upcoming 28 Day WholeFood Challenge course beginning in January 2024:Use the code: NatMedPodcast20We're born with a genetic blueprint, including some variations we may have acquired along the way. These variations, called SNPs (short for Single Nucleotide Polymorphisms), influence certain characteristics of our DNA blueprint to change gene expression. What we now know is that diet can have effects on gene expression  leading to powerful effects on our health.And what better clinician to lead us through how to master your genes using food, than Dr Denise Furness.Strap in and have the rewind button handy. This is an information-packed podcast!ReferencesMCM6 - lactoseMCM6 is located upstream from the LCT gene, which produces the enzyme lactase required to digest lactose. MCM6 influences LCT and lactase expression.PMID: 11788828, PMID: 12915462, PMID: 15114531HLA-DQ haplotypes - Gluten Human leukocyte antigen (HLA system) encodes the Major Histocompatibility Complex (MHC). These genes code for antigens (proteins) that help cells recognise self versus non-self. Genetic variations within HLA-DQA1 & HLA-DQB1 are linked to coeliac disease and other autoimmune conditions.PMID: 30763397, PMID: 29244800MTHFR FolateMTHFR converts 5,10-methylenetetrahydrofolate (5,10 methyleneTHF) to 5-methyltetrahydrofolate (5-MTHF). 5-MTHF is needed to convert homocysteine to methionine, therefore MTHFR supports methylation (making SAM) reactions throughout the body.MTHFR 677 T allele and increased risk for lower folate and higher homocysteine levels PMID: 25788000, 24091066, 7647779,  9545395 APO-E Alzheimer's, LipidsAPOE's main phenotypes are caused by the combination of two SNPs that combine to form the genotypes/isoforms of ε2, ε3 and ε4 or E2, E3, E4. The E4 allele is associated with higher LDL levels and cardiovascular and neurological complications. PMID: 25328986, PMID: 11882522SLC30A8 - zinc transporterSpecific to pancreatic islets and mainly expressed in β-cells that transport zinc from the cytoplasm into insulin secretory vesicles. Allelic variants have been associated with glucose and pro-insulin levels and confer susceptibility to insulin resistance and diabetes mellitus (T2DM). PMID: 28218639, 17463249, 30936916.FTO and MC4R - weight and obesityFat mass and obesity-associated gene (FTO)Melanocortin-4-receptor (MC4R) PMID: 31954858, 19079261, 26888713

Erectile dysfunction (ED) is a common and distressing condition that affects millions of men worldwide. It is characterized by the inability to achieve or maintain a firm erection sufficient for sexual intercourse. ED can be caused by various factors, including psychological issues, lifestyle choices, and underlying medical conditions.  You might have heard of ED, but you may not realize how common it is. Its prevalence tends to increase with age (if you're in your 40's, you have a 40% chance of experiencing ED, and this risk increases by about 10% with every decade of life).  Fortunately, there are several treatment options available to address ED, including pharmaceutical medications, lifestyle changes, and emerging therapies like peptide treatments.  In this podcast, we will explore the causes and traditional treatments of ED before delving into the exciting potential of peptide therapies in managing ED. What causes erectile dysfunction (ED)? Erectile dysfunction is a complex condition influenced by a variety of physical and psychological factors. To understand the potential benefits of peptide therapies, it's important to understand the underlying causes of ED. Psychological Factors: Psychological factors can significantly contribute to ED. Stress, anxiety, depression, and relationship problems can all lead to a temporary inability to achieve or maintain an erection. Counseling, therapy, and stress-reduction techniques are often effective in these cases. Lifestyle Choices: Unhealthy lifestyle choices, such as smoking, excessive alcohol consumption, a sedentary lifestyle, and a poor diet, can increase the risk of ED. Making healthier choices can lead to significant improvements in erectile function Underlying Medical Conditions: Numerous medical conditions are associated with ED, including: Cardiovascular disease: Conditions like atherosclerosis can restrict blood flow to the penis. While high blood pressure and high cholesterol can also cause ED. In fact, people with ED are often diagnosed with a heart condition less than 5 years later. Diabetes: High blood sugar levels can damage blood vessels and nerves, leading to ED. The longer you have diabetes, the more likely you are to experience ED. Neurological disorders: Conditions like multiple sclerosis and Parkinson's disease can affect nerve signals.  Mental health conditions: Depression, anxiety, high-stress levels can also play a role in your ability to maintain an erection.  Hormonal imbalances: Low testosterone levels can contribute to ED. About 40% of men older than 45 have low testosterone (low T). Obesity: Excess body fat can lead to hormonal imbalances (your body starts to turn testosterone into estrogen) and cardiovascular issues, both of which increase ED risk.  Medications: Certain medications, such as those used to treat pain, enlarged prostate, hypertension, depression, and acid reflux, may have ED as a side effect.  Aging: ED becomes more common as men age due to a natural decline in testosterone levels and changes in blood vessel function. What are traditional erectile dysfunction treatments? The treatment of ED typically begins with lifestyle modifications and, if necessary, progresses to medical interventions. Traditional treatment options include: Lifestyle Changes: Quitting smoking Reducing alcohol consumption Exercising regularly Adopting a healthy diet Managing stress through relaxation techniques or therapy Medications: Oral medications such as sildenafil (Viagra), tadalafil (Cialis), vardenafil, and avanafil (Stendra) are phosphodiesterase type 5 (PDE5) inhibitors. They work by increasing blood flow to the penis, helping men achieve and maintain erections. Intracavernosal injections: Medications like alprostadil can be injected directly into the penis to induce an erection. Urethral suppositories: Alprostadil can also be administered as a suppository inserted into the urethra. Vacuum Erection Devices: These are mechanical devices that create a vacuum around the penis, drawing blood into the area and causing an erection. A constriction band is used to maintain the erection. Penile Implants: In cases where other treatments are ineffective, surgically implanted devices can help men achieve and maintain an erection. There are inflatable and semi-rigid penile implants available. While these traditional treatments are effective for many men, they may not be suitable for everyone due to side effects, contraindications, or personal preferences. This has led to the exploration of novel therapies, including the use of peptides. Peptide therapies for erectile dysfunction In recent years, researchers have investigated the potential of peptides in addressing ED. These peptides work by targeting specific pathways and mechanisms involved in erectile function. Here are some promising peptide therapies for ED: Melanotan II (MT-II): Melanotan II is a synthetic peptide initially developed as a tanning agent. However, it has gained attention for its potential to improve sexual function. MT-II stimulates melanocortin receptors in the brain, which can lead to increased sexual desire and improved erectile function. PT-141 (Bremelanotide): PT-141 is another peptide that targets melanocortin receptors, specifically MC3R and MC4R. It has been shown to increase sexual arousal and improve erectile function in both men and women.  Kisspeptin: Kisspeptin is a peptide that plays a role in regulating reproductive hormones. Studies have shown that kisspeptin administration can increase testosterone levels and improve erectile function, making it a potential treatment option for ED. Thymosin Beta-4 (TB4): TB4 is a peptide that has shown promise in promoting tissue repair and regeneration. While not directly targeting erectile function, it may help improve erectile function by enhancing tissue health and blood flow to the penis. Vasoactive Intestinal Peptide (VIP): VIP is a peptide with vasodilatory properties, meaning it can relax blood vessels and increase blood flow. It has been investigated as a potential treatment for ED, particularly in cases where vascular issues contribute to the condition. While peptide therapies for ED show promise, there are several challenges and considerations: Limited Clinical Data: Many peptide therapies are still in the experimental stage, with limited clinical data available on their long-term safety and effectiveness. Individual Variability: The response to peptide therapies can vary among individuals, and not all men may experience the same level of improvement in erectile function. Cost: Peptide therapies may be more expensive than traditional medications, and insurance coverage may be limited. Regulatory Status: The regulatory status of peptide therapies for ED can vary by country, and some may not be approved for clinical use. It's important to recognize that peptide therapies for ED are still in the early stages of research and may not be suitable for everyone. Consulting with a healthcare provider is necessary to determine the most appropriate treatment approach, taking into consideration individual needs and circumstances. As research in this field continues to advance, we can look forward to more effective and tailored treatments for ED, ultimately improving the lives of those affected by this condition. Thanks again for listening to The Peptide Podcast, 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, and have a happy, healthy week! Pro Tips We're huge advocates of using daily greens in your routine to help with gut, skin, nail, bone, and joint health. We take AG1 (athletic greens) every day. Not only does it have vitamins, minerals, and a diverse range of whole-food sourced ingredients, but it also has probiotics to promote a healthy gut microbiome and adaptogens to help with focus and mood balance. It's vegan, paleo, and keto-friendly.

Time to geek out a little bit this week because who doesn't love to talk about the brain!? Naomi sits down with Dr. Rachel Ross of Albert Einstein College of Medicine to chat about her latest publication in Physiology & Behavior that examines how a specific receptor in the prefrontal cortex--the very front part of our brain--influences food-related decision making. Dr. Ross shares the implications of her findings in the mouse model and how it could shape future research directions in studying food intake and associated behaviors, including eating disorders. Paper Mentioned in the Episode:1. Ross et al., (2023). Prefrontal cortex melanocortin 4 receptors (MC4R) mediate food intake behavior in male mice. Physiol Behav. 269:114280.Remember to also check out Dr. Rachel Ross' lab website! Dr. Ross is currently seeking a postdoctoral fellow. Reach out to her for more info if interested: rachel.ross@einsteinmed.edu. Contact Picture Blurrfect:Twitter: @BlurrfectInstagram: @Picture_BlurrfectE-mail: naomi.charalambakis90@gmail.com 

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

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.06.28.546874v1?rss=1 Authors: Gui, Y., Dahir, N. S., Downing, G., Sweeney, P., Cone, R. D. Abstract: The melanocortin-3 receptor (MC3R) is a negative regulator of the central melanocortin circuitry via presynaptic expression on AgRP nerve terminals, from where it regulates GABA release onto secondary MC4R-expressing neurons. Hence, animals lacking MC3R (MC3R KO) exhibit hypersensitivity to MC4R agonists. However, MC3R KO mice also exhibit defective behavioral and neuroendocrine responses to fasting. Here, we demonstrate that MC3R KO mice exhibit defective activation of AgRP neurons in response to fasting and cold exposure, while exhibiting normal inhibition of AgRP neurons by sensory detection of food. Further, using an AgRP-specific MC3R knockout model, we show that the control of AgRP neuron activation by MC3R is cell-autonomous. One mechanism underlying this involves the response to ghrelin, which is also blunted in mice with AgRP-specific deletion of the MC3R. Thus, MC3R is a crucial player in the control of energy homeostasis by the central melanocortin system, not only acting presynaptically on AgRP neurons, but via AgRP cell-autonomous regulation of fasting- and cold-induced neuronal activation as well. 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/2022.12.01.518727v1?rss=1 Authors: Eliason, N. L., Pham, K., Varshney, R., Farriester, J. W., Lacy, C. I., Rice, H. C., Rudolph, M. C., Freeman, W. M., Sharpe, A. L. Abstract: World-wide, nearly 40% of the adult population is classified as clinically obese. Central inflammation is highly correlated with obesity and increases morbidity and deterioration of health. The hypothalamus is a brain region that governs many facets of energy homeostasis, and melanocortins in the hypothalamus both decrease feeding and increase metabolism via melanocortin-4 receptors (MC4Rs). Although MC4Rs are present on neurons and astrocytes (aMC4R) previous work has focused almost exclusively on the neuronal population with the contribution of aMC4R on these processes largely unknown. Our objective was to determine the effects of hypothalamic aMC4R deletion on central and peripheral inflammation, as well as feeding and body weight homeostasis. Adult MC4R fl/fl mice were microinjected with an astrocyte-specific promoter driving Cre-expression (AAV-GFAP-GFP-Cre) or AAV-control (AAV-GFAP-GFP; n=4-7/group/sex) to produce a hypothalamic knock-down of aMC4R (KD). Body weight and composition were monitored throughout the study, and indirect calorimetry was conducted at 1 and 4 weeks after AAV injection. Acquisition of operant self-administration of palatable food was also examined. Mice were euthanized 7-8 weeks post AAV injection and brain and tissue samples were collected. We observed a significant increase in body weight, feeding, and energy balance in the KD group compared to control group. Inflammation was significantly increased centrally in KD mice within the hypothalamus, but not peripherally within serum. Additionally, aMC4R KD mice trended towards an increased reward learning for palatable food. This is the first demonstration that hypothalamic aMC4R, independent of neuronal MC4R, is important in modulating inflammation as well as contributing to energy balance. These results provide an integral understanding of the aMC4R system that will provide the foundation for future studies investigating the role of aMC4R in various disease states. 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/2022.11.06.515311v1?rss=1 Authors: Nguyen, H. P., Chan, C. S., Cintron, D. L., Sheng, R., Harshman, L., Nobuhara, M., Ushiki, A., Biellak, C., An, K., Gordon, G. M., Mifsud, F., Blake, A., Huang, E. J., Hemberg, M., Vaisse, C., Ahituv, N. Abstract: Over 500 noncoding genomic loci are associated with obesity. The majority of these loci reside near genes that are expressed in the hypothalamus in specific neuronal subpopulations that regulate food intake, hindering the ability to identify and functionally characterize them. Here, we carried out integrative single-cell analysis (RNA/ATAC-seq) on both mouse and human male and female hypothalamus to characterize genes and regulatory elements in specific cell subpopulations. Utilizing both transcriptome and regulome data, we identify over 30 different neuronal and non-neuronal cell subpopulations and a shared core of transcription factors that regulate cell cluster-specific genes between mice and humans. We characterize several sex-specific differentially expressed genes and the regulatory elements that control them in specific cell subpopulations. Overlapping cell-specific scATAC peaks with obesity-associated GWAS variants, identifies potential obesity-associated regulatory elements. Using reporter assays and CRISPR editing, we show that many of these sequences, including the top obesity-associated loci (FTO and MC4R), are functional enhancers whose activity is altered due to the obesity-associated variant and regulate known obesity genes. Combined, our work provides a catalog of genes and regulatory elements in hypothalamus cell subpopulations and uses obesity to showcase how integrative single-cell sequencing can identify functional variants associated with hypothalamus-related phenotypes. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

 I've been asked frequently if I still do private coaching sessions. The answer is I do. I'm reframing how though.  I've had to guard my time to start, grow and manage a team where we not only offer the first and only exclusively made-for-menopause fitness membership in the world, I train trainers and health coaches so more women have optimal choices for the way they want to train and learn.   I've only had time to coach a handful of clients recently. I'm changing the way I coach to include a combination of private and group coaching sessions weekly. More touches, more accountability in less time weekly. You have access to workouts, workout protocols, and can use both the private and group sessions to have your questions answered. I will still have a few private slots for women who want complete anonymity and one-to-one, but as I coach more trainers and become more aware of the value of community, I'm pointed in this direction.  Is It the Right Time for You? For details just send me a message, to be first to know about the next group.   And then there's content like this, where my intent is that if you show up, no matter what your intention is… to simply stop in for a few tips you can use yourself or you want the structure and science-based proven steps, you will benefit from every podcast, blog or video that's available for free. There are thousands of pieces of content.  Everything I teach in my programs is out there in those free offers. For the person who can discipline their way through and apply, it's there.  So, no matter who you are, thanks for listening. I hope every piece of content is a valuable next step somehow on your journey.  I create these in the early mornings… my favorite time of day. I don't let many people into those moments… even my family know that. So, you're a favorite part of my day.  This podcast is like private coaching. In it:  What I'd ask and why. What I'd learn about you from the response.  Why you want to answer these questions for yourself  to consider a next “best step” in your own journey.  Coaching Client Questions:  How well are you sleeping?  How's your digestion and elimination?  What does a typical day of eating and drinking look like for you?  How much protein are you eating in a day?  What is the source of your protein? What is the timing of these meals with exercise and sleep?  Are you aware of your food tolerances and blood sugar responses to food?  Describe your last two weeks of exercise, what is that like? When you lift weights, how hard would you say you work?  How often are you lifting?  Do you do any interval training?  Do you like to track… steps, sleep, are you tracking macronutrients? Are you working with a physician, functional doctor, naturopath? Have you tested … micronutrients, hormones, gut? Are you taking HRT? Are you considering it, interested, curious about it?  Do you want to have a discussion about how it can help exercise results?  Right now, what's happening in your life, relationships, work … that you want to share so I have some insight about your other sources of stress? What Do I Learn About My Coaching Client? Each of these questions I ask my coaching client and train our Flipping 50 Menopause Fitness Specialists to ask and respond to in order to gather information that determines our first steps. A program leads a group of people through a fairly set step-by-step. Even though it may be a blueprint like the After 50 Fitness Formula for Women or the Food Flip addition to our STRONGER program, it's based on a group of women in menopause, not an individual.  So, of course one-on-one is more custom and focused on you.  What we're looking at in generally is based on some key things. There are some new emerging studies.. unfortunately you know I share research based on women in menopause. One here from 2022 is and a second is on mice. So, does it apply? Other studies -done on menopausal subjects - have suggested similar findings and stimulus. I'll explain more as I go over it.  Many of you are show it to me girls. I love that. I also encourage you to let your fingers do the research. Pub Med is just as available to you as to me. If you're unsure what you're reading and how to interpret studies, reach out, that's great conversation for our Facebook Insiders group. (flipping 50 insiders)   Metabolic Effects of Menopause  Between Pre, peri, and post menopause women body composition was better pre and progressively increased. Changes were most dramatic during perimenopause. That led researchers to conclude if you're in perimenopause, now is the best time to start.  Look though, starting now if you're not doing something is still a best time!  Fat oxidation – what allows release of fat for use as energy – was reduced in perimenopause and post menopause. The time to offset it with training is in perimenopause.  In prior content I've shared that woman tend to burn more fat for fuel during exercise (compared to men) anyway. But it will decline, and that is especially true if your stress level is preventing fat burning because you're in fat storage mode.   Surges of estrogen jump-start us to be more active. At least in mice.   And it's also been found that we may have fewer pleasure receptors in response to exercise. (shared in a previous Flipping 50 masterclass) That endorphin high you used to get may not be kicking in the same way it did. [That doesn't mean “more” volume or intensity will improve it. It just means you may have to find other ways to reinforce your habits.] Women who do gain weight after menopause tend to share these commonalities:  They exercise less or over train Poor sleep quality or quantity They consume too few calories, protein, or carbohydrate Diets high in sugar (wine or alcohol in general)  Inflammatory food consumption  They don't do strength training with the intent to gain lean muscle tissue (all workouts are not created equally)  I'm digging to learn whether based on life circumstance, hormone status (that don't require labs when signs & symptoms point clearly to a trained coach), the training and lifestyle habits that are going to improve results.  I'm also educating my coaching client so she's empowered to make better choices for herself. In every program from the 5 Day Flip, to the 10-Day Hot Not Bothered Challenge, all the way to our membership, it's about giving you the keys and knowledge to pivot daily.  Questions? I love to hear from you.  References  Gould, Lacey M. MA1; Gordon, Amanda N. BS1; Cabre, Hannah E. MS, RDN1, 2; Hoyle, Andrew T. BS1; Ryan, Eric D. PhD2, 3; Hackney, Anthony C. PhD, DSc2, 4; Smith-Ryan, Abbie E. PhD1, 2, 4 Metabolic effects of menopause: a cross-sectional characterization of body composition and exercise metabolism, Menopause: April 2022 - Volume 29 - Issue 4 - p 377-389 doi: 10.1097/GME.0000000000001932 Krause, W.C., Rodriguez, R., Gegenhuber, B. et al. Oestrogen engages brain MC4R signalling to drive physical activity in female mice. Nature 599, 131–135 (2021). https://doi.org/10.1038/s41586-021-04010-3 Resources:  STRONGER: Tone & Define: https://www.flippingfifty.com/getstronger Sleep Yourself Skinny: https://www.flippingfifty.com/sleep-yourself-skinny Continuous Blood Glucose Monitor: https://www.flippingfifty.com/glucose

Creating a following a long-term, sustainable eating plan, especially when it includes losing weight, doesn't have to be an impossible journey. It's all about working with three key strategies, finding the best long-term strategy for your body and goals, and knowing when you might want to be flexible or choose a different plan for different periods of your life.   Key Takeaways 3 Nutrition Strategies for Sustainable Weight Loss  Intuitive Eating Mindful Eating Macro Counting   Strategies for Sustainable Weight Loss Long-term, sustainable nutrition is possible. Weight loss is within your reach. And finding a solution to your eating habits is a very realistic goal. It comes down to picking the right strategy for you, your body, and your goals… and then knowing when you need to change it up. One thing I really want to stress is that once you lose more than 10% of your body fat, you need to reevaluate and recalculate your weight loss strategy. If you don't, you will actually be eating in either surplus calories or in maintenance mode - neither of which will let your body lose weight! First, I talk about Intuitive Eating. Intuitive Eating is the right strategy for you if you are working towards healing your relationship with your body and with food. With Intuitive Eating, we have to talk about satiety and the satiety gene, MC4R, which might make it harder for you to determine your own satiety.   Tracking or Estimating Macros for Empowered Eating The next strategy I discuss is Mindful Eating. Mindful eating uses a flexible macro-based approach that lets you use your best estimates of the food you eat. I find it helpful to track your food for a few days so that you can get a good idea of what each portion looks like. I also talk you through the ratio I use for protein, carbs, and fat. The final strategy I look at is full-blown Macro counting. Macro counting isn't for everyone as it does take time and dedication to ensure you're tracking your food correctly. But when it works, it works well and I find it very empowering to be in control of your food. My final thought, however, is that I think weight loss works best when you use a combination of all three weight-loss strategies. If you need a more flexible approach, like you're going on vacation, switch over to intuitive eating. If you need something a bit more structured, head into macro counting. The bottom line is that the way you eat should make you feel good and empowered and that it's sustainable! How have you tried to lose weight in the past? What worked or didn't work for you? Which of these three strategies do you think sounds the most sustainable for you and your goals? Let me know in the comments on the episode page!   In This Episode How to manage a long-term, sustainable eating plan [3:30] What happens if you lose more than 10% of your lean muscle mass at once [5:15] Who intuitive eating is good for [7:30] What you need to know about satiety and the satiety gene [9:30] The difference between mindful eating and intuitive eating [12:30] How to calculate your protein goal [16:00] How macro counting can be empowering [24:00] How to use all 3 nutrition strategies to support your nutrition through every stage of your life [30:00]   Quotes “We won't decrease our Basal Metabolic Rate as much if we maintain our lean muscle mass because lean muscle mass is more metabolically active.” [5:00] “When we're committing to intuitive eating, our goal is going to be one of the more compassionate goals. Finding love for our body, finding love for our food, and really being one in mind and body.” [7:15] “If we have trouble with satiety, we can actually calculate our macros just to see what our body would require to be where we currently are, and then we can see how much food that is. Then our brain can see how much food that is so we can get more of an advantage when we're figuring out when satiety would likely happen.” [11:41] “Macro counting is a way for me to discover the most accurate data on what works, as I compare it to my primary goal, and what doesn't work.” [25:25] “Macro counting is reserved for those who like to work their mindset with it. There will be some struggles. If you are doing/counting/tracking/following them, it is an extra step of effort. It's more of a layer. If you believe that it's impacting your time and that you're giving up a lot to do it, and then you don't see the results you want, potentially you will be frustrated. But, if we think about it this way, what if the results you're getting with the data you're inputting are what they are, and all you have to do is input different data for different results, things change a bit. Macro counting becomes much more neutral.” [29:24]   Resources Mentioned Join the Waitlist for Jumpstart Find Life Coaching for Women Physicians Online Check out the full episode page here Follow Dr. Ali Novitsky on Facebook | Instagram Subscribe to Life Coaching for Women Physicians on Apple Podcasts Podcast production by the team at Counterweight Creative   Related Episodes Episode 68. Siobhan Key on Sustainable Weightloss Episode 110. How Our Genes Impact our Jeans Episode 79. Do More of What Works

In Episode 24 of the Unpilled Podcast, Kashif goes 1-on-1 to discuss one of his most highly requested topics, weight & weight loss. Conversation points highlighted include satiety in the gut, satisfaction and gene MC4r, addiction, shifting environments, UCP1 Gene & Thermal Regulations, a deep dive into exercise, building muscle vs fat, cellulite reduction, metabolization of micronutrients, lack of sleep vs obesity, and more.Listen On:Spotify: https://open.spotify.com/show/46OaVEp...iTunes: https://podcasts.apple.com/us/podcast...SUBSCRIBE TO THE PODCAST ► ADD US ON INSTAGRAM:Kashif: https://www.instagram.com/kashkhanofficial/DNA Company: https://www.instagram.com/thednacoWebsite:https://www.thednacompany.com/

In Episode 21 of The Unpilled Podcast, Kashif once again goes one-on-one answering your questions, with the focus being on Food and Diet. Topics discussed include the origins of farming, modern agriculture, how food affects behaviour, the development of bread, rice then vs now, a discussion on poultry, hunger coping mechanisms, the concept of satiety and gene MC4R, solutions for satisfaction, the importance of the microbiome, the gene FUT2 and gut health, and if fruit is good or bad.Listen On:Spotify: https://open.spotify.com/show/46OaVEp...iTunes: https://podcasts.apple.com/us/podcast...SUBSCRIBE TO THE PODCAST ► ADD US ON INSTAGRAM:Kashif: https://www.instagram.com/kashkhanofficialDNA Company: https://www.instagram.com/thednacoWebsite:https://www.thednacompany.com/

Did you know that redheads can tolerate more spicy foods than those with dark hair? This is supported by biology and genetics.  Ask any anesthesiologist or a dentist and they'll tell you - often with a sigh, I might add - that taking care of redhead is can be challenging! The issue of pain perception, tolerance, response to pain and  response to different classes of medications is a complicated and murky one when it comes to people with natural red hair.   Join me in this episode to learn about the evidence we have for complexity of pain and its management in redheads, recent emerging evidence that explains why and more importantly how to effectively navigate this complexity, ensuring safe and effective care of these patients.   Takeaways in This Episode When an anesthesiologist or a dentist see a redhead Why redheads have more dental problems and toothaches Why redheads sometimes need more pain medications and at other times need less Variability in pain responses amongst redheads The redhead gene and its implications Do redhead really tolerate more spicy foods than others? Do they bleed more compared to others with darker hair? Recent study providing insights about the genetics and reasons for differences in their pain perception, responses and treatments What do Melanocortin, MC1R, MC4R have to do with pain How you reconcile the different, complex and sometimes murky findings and provide safe and effective pain care  for redheads Links Proactive Pain Solutions Other Helpful Episodes on Opioid Safety Episode#30 . Ensuring Opioid Safety for Children and Teens with Rita Agarwal, MD Episode# 29. Opioid Stewardship: Responsible Pediatric Pain Care! with Benjamin Lee, MD Proactive Pain Solutions Physicians Academy Clinicians Pain Evaluation Toolkit

Estrogen signaling in arcuate Kiss1 neurons suppresses a sex-dependent female circuit promoting dense strong bones, Oestrogen engages brain MC4R signaling to drive physical activity in female mice, and LRH-1 mitigates intestinal inflammatory disease by maintaining epithelial homeostasis and cell survival Scientific Sense ® by Gill Eapen: Prof. Holly Ingraham who is Professor of Cellular Molecular Pharmacology at UCSF. Her research focuses on the basic science of "Hormones and Nerves in Female Physiology" aimed at improving women's health. --- Send in a voice message: https://anchor.fm/scientificsense/message

A 57-year-old male CEO, with problems with memory. Pt has borderline blood pressure.  Problems with memory started with taking a statin.  Pt also has issues with borderline blood sugar HGA1C is 5.8  and bloating.    Loses weight by avoiding fats and carbs   Patient's top objectives  1. Memory 2. Borderline blood sugar 3. Borderline blood pressure   Cardio Panel: ·       SLCO1B1(rs4149056) ·       ACE (rs4343) ·       AGT (rs699) ·       CYP1A2 (rs762551) ·       LIPC (rs1800588) ·        PPARD(rs2016520 Metabolic Panel ·       MC4R(rs17782313) ·       FTO (rs9939609)   Resources Nutrigenomics Case Study Events 2021  GMOTG Events Line-up PureGenomics Schedule a complimentary 1:1 Welcome to PureGenomics coaching session

以色列魏茨曼科学研究所领导的国际研究团队在《Science》上发表了一篇论文，研究表明了饥饿总开关黑皮质素受体4（MC4R）的激活机制--当该受体打开时，人们感到饱腹感；反之则是饥饿感。

以色列魏茨曼科学研究所领导的国际研究团队在《Science》上发表了一篇论文，研究表明了饥饿总开关黑皮质素受体4（MC4R）的激活机制--当该受体打开时，人们感到饱腹感；反之则是饥饿感。

以色列魏茨曼科学研究所领导的国际研究团队在《Science》上发表了一篇论文，研究表明了饥饿总开关黑皮质素受体4（MC4R）的激活机制--当该受体打开时，人们感到饱腹感；反之则是饥饿感。

Sars Cov2, as the Covid19 coronavirus is called, probably began as the vast majority of new diseases do, when an animal virus infected a person – perhaps in a market or farm. There’s a large animal market in the city of Wuhan that sold wild as well as farmed animals, and studies have shown that different species of animals can infect each other with coronaviruses on their journey to market. But there’s also a possibility that the virus originated in one of two government laboratories in Wuhan. After all, we know that other viruses have escaped from labs, including the original Sars virus, which escaped multiple times from different Asian labs. Jonathan Ball, Professor of Virology at the University of Nottingham, discusses with Gaia Vince why the lab leak theory is again in the news. We know that obesity runs in families but because parents and children live in the same environment and eat the same food it is difficult to tease out how much of this relationship is inherited genetically. Researchers at Cambridge University have been working with the Children of the 90s cohort of people based in Bristol, and they’ve have found that a mutation in a single gene drives obesity in some families. The gene in question is called MC4R. Professor Stephen O’Rahilly, who is one of the researchers, explains that the mutation is remarkably common and has a significant impact on individuals, from an early age. Last week, researchers released the biggest and most detailed map of how matter and dark matter have spread across the universe since the Big Bang. The problem, is that the dark matter is more smoothly distributed than expected according to Einstein’s theory. Some are now saying physics is broken. Was Einstein wrong? Astrophysicist Catherine Heymans, who is a Dark Universe expert, and has just been appointed Astronomer Royal for Scotland, the first woman to hold the role, talks about the implications of the new map of dark matter and her plans to encourage the public to appreciate the night sky. For the first time figurative rock art over 4000 years old has been discovered in Scotland. Up till now all that’s been found have been marks such as cups and rings. The new images are detailed portraits of deer, with antlers, on a capstone of a burial mound, or cairn, in Kilmartin Glen on the west coast. It’s a well-studied archaeological site but the rock art hadn’t been spotted before. Gaia asked Tertia Barnett, Principal Investigator for Scotland’s Rock Art Project at Historic Environment Scotland, about who may have produced this art.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.11.13.382325v1?rss=1 Authors: Bernard, A. A., Ojeda Naharros, I., Bourgain-Guglielmetti, F., Ciprin, J., Yue, X., Zhang, S., McDaid, E., Nachury, M. V., Reiter, J., Vaisse, C. Abstract: The G protein-coupled receptor MC4R (Melanocortin-4 Receptor) and its associated protein MRAP2 (Melanocortin Receptor-Associated Protein 2) are both essential for the regulation of food intake and body weight in humans and mice. MC4R localizes and functions at the neuronal primary cilium, a microtubule-based organelle that senses and relays extracellular signals. Here, we demonstrate that MRAP2 is critical for the ciliary localization and weight-regulating function of MC4R. Our data reveal that GPCR localization to primary cilia can require specific accessory proteins that may not be present in heterologous cell systems. Our findings also demonstrate the essential role of neuronal primary cilia localization of MC4R for adequate control of energy homeostasis and the obesity-promoting effect of genetic disruption of this pathway. Copy rights belong to original authors. Visit the link for more info

Episode Notes Rhythm Pharmaceuticals is tackling rare genetic obesity disorders with their MC4R agonist, Setmelanotide. They have 3 upcoming catalysts, the most important being the effect of the compound on a basket of high impact "loss of function" patients (POMC/LEPR-deficient heterozygotes, in particular). I go through all their catalysts in great detail along with a mock model. Biogen's Aducanumab was decidedly voted against in a recent FDA advisory committee with regards to the evidence provided in support of an effect in Alzheimer's disease. The stock saw serious volatility after the FDA briefing documents were released, but has since subsided with a CRL likely being priced in. I also touch on $AXGT ($SIOX) and $ATNM. 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

This episode featuring Dr. Penny Kendall-Reed explores how clinicians can use genetics to inform patients in their weight management journey. We discuss how certain hormones and SNPs can determine the best diet and what “eating healthy” really means for each individual. We share practical advice for providers to identify which variants to reference that play a role in regulating the metabolic hormones that influence hunger and satiety. Key Takeaways: [0:51] We get a much better result of managing mood and weight when we first determine the underlying genetic drivers that influence appetite and satiety. [3:08] Dr. Nathan Morris shares a story that shows the importance of understanding the relationship between dopamine and serotonin with mood and food. He highlights the connection between our genetic variations and how they affect our eating behaviors weight. [12:39] Ghrelin is a hormone that increases appetite and also plays a role in our weight. Leptin decreases our appetite and lets us know when we are full and satiated. [INSERT] FTO plays a role in the production of these and has a big impact on our metabolism. FTO does not like simple sugar or saturated fats, and when you are variant with FTO you are likely to burn fat slower and not feel full. It is especially important to look for FTO before recommending the ketogenic or paleo diet. [15:48] With MC4R gene variant, there is a 43% increased chance of obesity. Patients with variant MC4R have often struggled with weight management, and despite trying different diets, they have a hard time with finding long term success. [17:45] FTO and MC4R are both influenced by the dopaminergic pathways. Their activity influences ghrelin, which can cause patients to become constant snackers seeking a dopamine hit. This relationship with dopamine means it is important to also look at the DRD2 (dopamine receptor) of patients to make sure their dopamine uptake is working properly. [18:53] FTO will also dictate how much protein we need per meal, the A/A risk variant, with the slowest metabolic position typically needs the highest amount of protein. [20:20] Those with the MC4R gene variant may have dealt with childhood obesity and struggled just trying to find balance most of their life. Dr. Penny suggests diet and exercise alone won’t always work, and we can benefit from treating this using a supplemental protocol including a combination of Piper betle, Dolichos biflorus, and acetyl-L-carnitine. [21:58] Leptin is our metabolic hormone which signals when we have had enough to eat. When we are constantly snacking, leptin may build resistance and prevent us from feeling full. Intermittent fasting may work well for patients as a way to help combat leptin resistance.  [23:03] The APOA2 gene variant also affects these metabolic hormones and when Dr. Penny sees this she recommends the patient eats under 22 grams of saturated fat a day. [26:02] Understanding how genetic variations play a role in our mood and weight management takes away the guilt people feel and realize they have control over it. When they feel better and have a road map of what eating right really looks like for them personally, they are more likely to see good results and stick to their plan. This transforms food from a burden to a gift and pleasure. Mentioned: Good Medicine Pure Encapsulations PureGenomics Free PureGenomics Business Integration 30-minute consult. Schedule Here Ep 2 - First Things First, Mental Health Ep 5 - Feeding on Fear with Morgan Knull of Feed Your Genes Dr. Penny Kendall-Reed PKR Health   Quotes: “Eat right really is generic advice that gives no clue to the patient of what that means.” - Dr. Nathan Morris “We are in some way enslaved to these hormones. It’s almost irrational what they make you want to do.” - Dr. Nathan Morris “We have our DNA which is our nature, but we can nurture it to be able to express optimal function.” - Dr. Kara Ware

On today's show I talk about MC4R, it's link to OCD and obesity, and how you can use mindfulness to win the battle against your own mind. For today's show notes, just go to http://www.killingafatguy.com/shownotes. There I share links to some great resources that can help you begin your own journey. If you'd like to be a guest on the Killing A Fat Guy Show, head on over to http://www.killingafatguy.com/killing-a-fat-guy-show-registration For a copy of my book, just go to http://www.killingafatguybook.com --- Support this podcast: https://anchor.fm/killingafatguy/support

In der deutschen Bevölkerung leidet, bezogen auf den BMI (Body-Mass-Index), etwa jeder zweite an Übergewicht. Innerhalb dieser Gruppe müssen dabei über 25 % als krankhaft adipös eingestuft werden. Trotz der weiten Verbreitung, ist zurzeit weder eine erfolgreiche medikamentöse Therapie der Adipositas verfügbar, noch sind die grundlegenden Mechanismen der Gewichtsregulation vollständig verstanden. Der MC4R (Melanocortin-4-Rezeptor) und sein Ligand α-MSH (melanocyte-stimulating hormone) stellen einen entscheidenden Punkt bei der Energieregulation des Körpers dar und sind damit eine vielversprechende pharmakologische Zielstruktur zur Behandlung von Adipositas. Trotz der enormen Bedeutung dieses Rezeptors ist bemerkenswert wenig über die MC4R-induzierten Signalwege bekannt. Ziel dieser Arbeit war es, α MSH-induzierte anorexigene Signal¬wege in murinen hypothalamischen Zellen (GT1 7), die den MC4R endogen exprimieren, zu identifizieren und zu charakterisieren. In dieser Arbeit konnte mit hochspezifischen Antikörpern gezeigt werden, dass nach 20 h Serumentzug die Stimulation von GT1-7 Zellen mit α MSH die cAMP-abhängige PKA (Proteinkinase A) aktiviert und somit zu einer ERK-1/2 (extracellular signal-regulated kinase-1/2) Phosphorylierung führt. Die aktivierte ERK-1/2 inhibiert anschließend die konstitutiv aktive AMPK-Kinase LKB1 (liver kinase B1), was in einer verminderten Phosphorylierung der nach¬geschalteten AMPK (AMP-activated protein kinase) an Threonin 172 resultiert. Damit ergibt sich eine lineare α-MSH-induzierte Signalkaskade, bei der die AMPK Dephosphorylierung von PKA, ERK-1/2 und LKB1 abhängig ist. Die Durchführung von Versuchen nach mehrstündigem Serumentzug ist zwar etabliert, führt aber zu Veränderungen in der Zelle, die sich unter anderem auf Proliferation und Morphologie auswirken. Da unklar ist, welche Versuchs¬bedingungen dem physiologischen Zustand eines Neurons entsprechen, wurde die α MSH-induzierte Signalkaskade zusätzlich unter serumhaltigen Bedingungen untersucht. Dabei führt die Stimulation mit α-MSH immer noch zu einer Aktivierung der ERK-1/2 und auch zu einer Dephosphorylierung der AMPK, letzteres allerdings unabhängig von PKA und ERK-1/2. Des Weiteren wird die AMPK nicht mehr exklusiv durch LKB1 reguliert, sondern die AMPK-Kinase TAK1 (TGF-β-activated kinase-1) spielt ebenfalls eine Rolle. Erste Hinweise aus einem Kinase-Aktivitäts-Array deuten daraufhin, dass diese Unterschiede in einer distinkten ERK-1/2 Aktivierung, über Rap-1 unter serumfreien oder über K-Ras unter serumhaltigen Bedingungen, begründet sein könnten. Diese Dissertation soll zu einem besseren Verständnis von anorexigenen Signal-wegen im Hypothalamus beitragen und könnte bei der Generierung neuer Anti Adipositas Medikamente hilfreich sein.

Meta-analyses of population-based genome-wide association studies (GWAS) in adults have recently led to the detection of new genetic loci for obesity. Here we aimed to discover additional obesity loci in extremely obese children and adolescents. We also investigated if these results generalize by estimating the effects of these obesity loci in adults and in population-based samples including both children and adults. We jointly analysed two GWAS of 2,258 individuals and followed-up the best, according to lowest p-values, 44 single nucleotide polymorphisms (SNP) from 21 genomic regions in 3,141 individuals. After this DISCOVERY step, we explored if the findings derived from the extremely obese children and adolescents (10 SNPs from 5 genomic regions) generalized to (i) the population level and (ii) to adults by genotyping another 31,182 individuals (GENERALIZATION step). Apart from previously identified FTO, MC4R, and TMEM18, we detected two new loci for obesity: one in SDCCAG8 (serologically defined colon cancer antigen 8 gene; p = 1.85610 x 10(-8) in the DISCOVERY step) and one between TNKS (tankyrase, TRF1-interacting ankyrin-related ADP-ribose polymerase gene) and MSRA (methionine sulfoxide reductase A gene; p = 4.84 x 10(-7)), the latter finding being limited to children and adolescents as demonstrated in the GENERALIZATION step. The odds ratios for early-onset obesity were estimated at similar to 1.10 per risk allele for both loci. Interestingly, the TNKS/MSRA locus has recently been found to be associated with adult waist circumference. In summary, we have completed a meta-analysis of two GWAS which both focus on extremely obese children and adolescents and replicated our findings in a large followed-up data set. We observed that genetic variants in or near FTO, MC4R, TMEM18, SDCCAG8, and TNKS/MSRA were robustly associated with early-onset obesity. We conclude that the currently known major common variants related to obesity overlap to a substantial degree between children and adults.

More than 70 missense mutations have been identified in the human melanocortin 4 receptor (MC4R), and many of them have been associated with obesity. In a number of cases, the causal link between mutations in MC4R and obesity is controversially discussed. Here, we mined evolution as an additional source of structural information that may help to evaluate the functional relevance of naturally occurring variations in MC4R. The sequence information of more than 60 MC4R orthologs enabled us to identify residues that are important for maintaining receptor function. More than 90% of all inactivating mutations found in obese patients were located at amino acid positions that are highly conserved during 450 million years of MC4R evolution in vertebrates. However, for a reasonable number of MC4R variants, we found no correlation between structural conservation of the mutated position and the reported functional consequence. By re-evaluating selected mutations in the MC4R, we demonstrate the usefulness of combining functional and evolutionary approaches.

We initially performed a mutation screen of the coding region of the MC4R in 808 extremely obese children and adolescents and 327 underweight or normal-weight controls allowing for a case-control study. A total of 16 different missense, nonsense, and frameshift mutations were found in the obese study group; five of these have not been observed previously. In vitro assays revealed that nine [the haplotype (Y35X; D37V) was counted as one mutation] of the 16 mutations led to impaired cAMP responses, compared with wild-type receptor constructs. In contrast, only one novel missense mutation was detected in the controls, which did not alter receptor function. The association test based on functionally relevant mutations was positive (P = 0.006, Fisher's exact test, one-sided). We proceeded by screening a total of 1040 parents of 520 of the aforementioned obese young index patients to perform transmission disequilibrium tests. The 11 parental carriers of functionally relevant mutations transmitted the mutation in 81.8% (P = 0.033; exact one-sided McNemar test). These results support the hypothesis that these MC4R mutations represent major gene effects for obesity.