Podcasts about pparg

This month on Episode 42 of Discover CircRes, host Cynthia St. Hilaire highlights four original research articles featured in the October 28 and November 11th  issues of Circulation Research. This episode also features an interview with Dr Miguel Lopez-Ramirez and undergraduate student Bliss Nelson from University of California San Diego about their study, Neuroinflammation Plays a Critical Role in Cerebral Cavernous Malformations.   Article highlights:   Jia, et al. Prohibitin2 Maintains VSMC Contractile Phenotype   Rammah, et al. PPARg and Non-Canonical NOTCH Signaling in the OFT   Wang, et al. Histone Lactylation in Myocardial Infarction   Katsuki, et al. PCSK9 Promotes Vein Graft Lesion Development   Cindy St. Hilaire:        Hi, and welcome to Discover CircRes, the podcast of the American Heart Association's Journal, Circulation Research. I'm your host, Dr Cindy St. Hilaire from the Vascular Medicine Institute at the University of Pittsburgh, and today, I'm going to be highlighting articles from our October 28th and our November 11th issues of Circ Res. I'm also going to have a chat with Dr Miguel Lopez-Ramirez and undergraduate student Bliss Nelson, about their study, Neuroinflammation Plays a Critical Role in Cerebral Cavernous Malformations. But, before I get into the interviews, here are a few article highlights.   Cindy St. Hilaire:        The first article is from our October 28th issue, and the title is, PHB2 Maintains the Contractile Phenotype of Smooth Muscle Cells by Counteracting PKM Splicing. The corresponding author is Wei Kong, and the first authors are Yiting Jia and Chengfeng Mao, and they are all from Peking University. Insults to blood vessels, whether in the form of atherosclerosis, physical injury, or inflammation, can trigger vascular smooth muscle cells to transition from a contractile state to a proliferative and migratory one. Accompanying this conversion is a switch in the cells' metabolism from the mitochondria to glycolysis. But what controls this switch? To investigate, this group compared the transcriptomes of contractile and proliferative smooth muscle cells.   Among the differentially expressed genes, more than 1800 were reciprocally up and down regulated. Of those, six were associated with glucose metabolism, including one called Prohibitin-2, or PHB2, which the team showed localized to the artery wall. In cultured smooth muscle cells, suppression of PHB2 reduced expression of several contractile genes. While in rat arteries, injury caused a decrease in production of PHB2 itself, and of contractile markers.   Furthermore, expression of PHB2 in proliferative smooth muscle cells could revert these cells to a contractile phenotype. Further experiments revealed PHB2 controlled the splicing of the metabolic enzyme to up-regulate the phenotypic switch. Regardless of mechanism, the results suggest that boosting PHB2 might be a way to reduce adverse smooth muscle cell overgrowth and conditions such as atherosclerosis and restenosis.   Cindy St. Hilaire:        The second article I'm going to highlight is also from our October 28th issue, and the first authors are Mayassa Rammah and Magali Theveniau-Ruissy. And the corresponding authors are Francesca Rochais and Robert Kelly. And they are all from Marseille University. Abnormal development of the heart's outflow track, which ultimately forms the bases of the aorta and the pulmonary artery, accounts for more than 30% of all human congenital heart defects. To gain a better understanding of outflow tract development, and thus the origins of such defects, this group investigated the role of transcription factors thought to be involved in specifying the superior outflow tract, or SOFT, which gives rise to the subaortic myocardium, and the inferior outflow tract, which gives rise to the subpulmonary myocardium. Transcription factor S1 is over-expressed in superior outflow tract cells and the transcription factors, TBX1 and PPAR gamma, are expressed in inferior outflow tract cells.   And now this group has shown that TBX1 drives PPAR gamma expression in the inferior outflow tract, while Hess-1 surpasses PPAR gamma expression in the superior outflow tract. Indeed, in mouse embryos lacking TBX1, PPAR gamma expression was absent in the outflow tract. While in mouse embryos lacking Hess-1, PPAR gamma expression was increased and PPAR gamma positive cells were more widespread in the outflow tract.   The team also identified that signaling kinase DLK is an upstream activator of Hess-1 and a suppressor of PPAR gamma. In further detailing the molecular interplay regulating outflow tract patterning, the work will shed light on congenital heart disease etiologies, and inform potential interventions for future therapies.   Cindy St. Hilaire:        The third article I want to highlight is from our November 11th issue of Circulation Research, and the title is Histone Lactylation Boosts Reparative Gene Activation Post Myocardial Infarction. The first author is Jinjin Wang and the corresponding author is Maomao Zhang, and they're from Harbin Medical University. Lactylation of histones is a recently discovered epigenetic modification that regulates gene expression in a variety of biological processes. In inflammation, for example, a significant increase in histone lactylation is responsible for switching on reparative genes and macrophages when pro-inflammatory processes give way to pro-resolvin ones.   The role of histone lactylation in inflammation resolution has been shown in a variety of pathologies, but has not been examined in myocardial infarction. Wang and colleagues have now done just that. They isolated monocytes from the bone marrow and the circulation of mice at various time points after induced myocardial infarctions, and examined the cells' gene expression patterns. Within a day of myocardial infarction, monocytes from both bone marrow and the blood had begun upregulating genes involved in inflammation resolution. And, concordant with this, histone lactylation was dramatically increased in the cells, specifically at genes involved in repair processes.   The team went on to show that injection of sodium lactate into mice boosted monocyte histone lactylation and improved heart function after myocardial infarction, findings that suggest further studies of lactylation's pro-resolving benefits are warranted. Cindy St. Hilaire:        The last article I want to highlight is titled, PCSK9 Promotes Macrophage Activation via LDL Receptor Independent Mechanisms. The first authors are Shunsuke Katsuki and Prabhash Kumar Jha, and the corresponding author is Masanori Aikawa, and they are from Brigham and Women's Hospital in Harvard. Statins are the go-to drug for lowering cholesterol in atherosclerosis patients. But the more recently approved PCSK9 inhibitors also lower cholesterol and can be used to augment or replace statins in patients where these drugs are insufficient.   PCSK9 is an enzyme that circulates in the blood and destroys the LDL receptor, thereby impeding the removal of bad cholesterol. The enzyme also appears to promote inflammation, thus potentially contributing to atherosclerosis in two ways. This group now confirms that PCSK9 does indeed promote pro-inflammatory macrophage activation and lesion development, and does so independent of its actions on the LDL receptor.   The team assessed PCSK9-induced lesions in animals with saphenous vein grafts, which are commonly used in bypass surgery but are prone to lesion regrowth. They found that LDL receptor lacking graft containing mice had greater graft macrophage accumulation and lesion development when PCSK9 activity was boosted than when it was not. The animal's macrophages also had higher levels of the pro-inflammatory factor expression. Together, this work shows that PCSK9 inhibitors provide a double punch against atherosclerosis and might be effective drugs for preventing the all too common failure of saphenous vein grafts.   Cindy St. Hilaire:        So, today with me I have Dr Miguel Lopez-Ramirez and undergraduate student Bliss Nelson from the University of California in San Diego, and we're going to talk about their study, Neuroinflammation Plays a Critical Role in Cerebral Cavernous Malformation Disease, and this article is in our November 11th  issue of Circulation Research. Thank you both so much for joining me today. Before we talk about the science, want to just maybe tell me a little bit about yourselves?   Bliss Nelson:                My name is Bliss Nelson. I'm a member of Miguel Lopez-Ramirez's lab here at UC San Diego at the School of Medicine. I'm an undergraduate student here at UC San Diego. I'm actually a transfer student. I went to a community college here in California and I got involved in research after I transferred.   Cindy St. Hilaire:        What's your major?   Bliss Nelson:                I'm a cognitive science major.   Cindy St. Hilaire:        Excellent. You might be the first undergrad on the podcast, which is exciting.   Bliss Nelson:                Wow. What an honor. Thank so much.   Cindy St. Hilaire:        And Miguel, how about you?   Miguel Lopez-Ramirez: Yes, thank you. Well, first thank you very much for the opportunity to present our work through this media. It's very exciting for us. My name is Miguel Alejandro Lopez-Ramirez, and I'm an assistant professor in the Department of Medicine and Pharmacology here at UCSD. Cindy St. Hilaire:        Wonderful. I loved your paper, because, well, first, I don't think I've talked about cerebral cavernous malformations. So what are CCMs, and why are they so bad?   Bliss Nelson:                Cerebral cavernous malformations, or CCMs for short, are common neurovascular lesions caused by a loss of function mutation in one of three genes. These genes are KRIT1, or CCM1, CCM2 and PDCD10, or CCM3, and generally regarded as an endothelial cell autonomous disease found in the central nervous system, so the brain and the spinal cord.   The relevance of CCMs is that it affects about one in every 200 children and adults, and this causes a lifelong risk of chronic and acute hemorrhaging. CCMs can be quiescent or dynamic lesions. If they are dynamic, they can enlarge, regress, or behave progressively, producing repetitive hemorrhaging and exacerbations of the disease.   Other side effects of the disease could be chronic bleedings, focal neurological deficits, headaches, epileptic seizures and, in some cases, death. There's no pharmacological treatment for CCMs. There's only one type of option some patients may have, which would be to have surgery to cut out the lesions. But of course this depends on where the lesion or lesions are in the central nervous system, if that's even an option. So sometimes there's no option these patients have, there's no treatment, which is what propels our lab to towards finding a pharmacological treatment or uncovering some of the mechanisms behind that.   Cindy St. Hilaire:        Do people who have CCM know that they have them or sometimes it not detected? And when it is detected, what are the symptoms?   Bliss Nelson:                Sometimes patients who have them may not show any symptoms either ever in their lifetime or until a certain point, so really the only way to find out if you were to have them is if you went to go get a brain scan, if you went to go see a doctor, or if you started having symptoms. But also, one of the issues with CCMs is that they're very hard to diagnose, and in the medical community there's a lack of knowledge for CCMs, so sometimes you may not get directed to the right specialist in time, or even ever, and be diagnosed.   Miguel Lopez-Ramirez: I will just add a little bit. It is fabulous, what you're doing. I think this is very, very good. But yes, that's why they're considered rare disease, because it's not obvious disease, so sometimes most of the patient, they go asymptomatic even when they have one lesions, but there's still no answers of why patients that are asymptomatics can become symptomatics. And there is a lot in neuro study, this study that we will start mentioning a little bit more in detail. We try to explain these transitions from silent or, quiescent, lesion, into a more active lesion that gives the disability to the patient.   Some of the symptoms, it can start even with headaches, or, in some cases, they have more neurological deficits that could be like weakness in the arms or loss of vision. In many cases also problems with the speech or balance. So it depends where the lesion is present, in the brain or in the spinal cord, the symptoms that the patient will experience. And some of the most, I will say, severe symptoms is the hemorrhagic stroke and the vascular thrombosis and seizure that the patients can present. Those would be the most significant symptoms that the patient will experience.   Cindy St. Hilaire:        What have been some limitations in the study of CCMs? What have been limitations in trying to figure out what's going on here?   Bliss Nelson:                The limitations to the disease is that, well, one, the propensity for lesions, or the disease, to come about, isn't known, so a lot of the labs that work on it, just going down to the basic building blocks of what's even happening in the disease is a major problem, because until that's well established, it's really hard to go over to the pharmacological side of treating the disease or helping patients with the disease, without knowing what's going on at the molecular level.   Cindy St. Hilaire:        You just mentioned molecular level. Maybe let's take a step back. What's actually going on at the cellular level in CCMs? What are the major cell types that are not happy, that shift and become unhappy cells? Which are the key players?   Bliss Nelson:                That's a great question and a great part of this paper. So when we're talking about the neuroinflammation in the disease, our paper, we're reporting the interactions between the endothelium, the astrocytes, leukocytes, microglia and neutrophils, and we've actually coined this term as the CaLM interaction.   Cindy St. Hilaire:        Great name, by the way.   Bliss Nelson:                Thank you. All props to Miguel. And if you look at our paper, in figure seven we actually have a great graphic that's showing this interaction in play, showing the different components happening and the different cell types involved in the CaLM interaction that's happening within or around the CCM lesions.   Cindy St. Hilaire:        What does a astrocyte normally do? I think our podcast listening base is definitely well versed in probably endothelial and smooth muscle cell and pericyte, but not many of us, not going to lie, including me, really know what a astrocyte does. So what does that cell do and why do we care about its interaction with the endothelium?   Miguel Lopez-Ramirez: Well, the astrocytes play a very important role. Actually, there are more astrocytes than any other cells in the central nervous system, so that can tell you how important they are. Obviously play a very important role maintaining the neurological synapses, maintaining also the hemostasis of the central nervous system by supporting not only the neurons during the neural communication, but also by supporting the blood vessels of the brain.   All this is telling us that also another important role is the inflammation, or the response to damage. So in this case, what also this study proposed, is that new signature for these reactive astrocytes during cerebral malformation disease. So understanding better how the vasculature with malformations can activate the astrocytes, and how the astrocytes can contribute back to these developing of malformations. It will teach us a lot of how new therapeutic targets can be implemented for the disease.   This is part of this work, and now we extend it to see how it can also contribute to the communication with immune cells as Bliss already mentioned.   Cindy St. Hilaire:        Is it a fair analogy to say that a astrocyte is more similar to a pericyte in the periphery? Is that accurate?   Miguel Lopez-Ramirez: No, actually there are pericytes in the central nervous system as well. They have different roles. The pericyte is still a neuron cell that give the shape, plays a role in the contractility and maintains the integrity of the vessels, while the astrocyte is more like part of the immune system, but also part of the supporting of growth factors or maintaining if something leaks out of the vasculature to be able to capture that.   Cindy St. Hilaire:        You used a handful of really interesting mouse models to conduct this study. Can you tell us a little bit about, I guess, the base model for CCM and then some of the unique tools that you used to study the cells specifically?   Bliss Nelson:                Yeah, of course. I do a lot of the animal work in the lab. I'd love to tell you about the mouse model. So to this study we use the animal model with CCM3 mutation. We use this one because it is the most aggressive form of CCM and it really gives us a wide range of options to study the disease super intricately. We use tamoxifen-regulated Cre recombinase under the control of brain endothelial specific promoter, driving the silencing of the gene CCM3, which we call the PDCD10 betco animal, as you can see in our manuscript. To this, the animal without the Cre system, that does not develop any lesions, that we use as a control, we call the PDCD10 plox. And these animals are injected with the tamoxifen postnatally day one, and then for brain collection to investigate, wcollected at different stages. So we do P15, which we call the acute stage, P50, which we term the progressive stage, and then P80, which is the chronocytes stage. And after enough brain collections, we use them for histology, gene expression, RNA analysis, flow cytometry, and different imaging to help us further look into CCMs.   Cindy St. Hilaire:        How similar is a murine CCM to a human CCM? Is there really good overlap or are there some differences?   Miguel Lopez-Ramirez: Yes. So, actually, that's a very good question, and that's part of the work that we are doing. This model definitely has advantages in which the lesions of the vascular formations are in an adult and juvenile animals, which represent an advantage for the field in which now we will be able to test pharmacological therapies in a more meaningful, way where we can test different doses, different, again, approaches. But definitely, I mean, I think I cannot say that it's only one perfect model for to mimic the human disease. It's the complementary of multiple models that give us certain advantages in another, so the integration of this knowledge is what will help us to understand better the disease.   Cindy St. Hilaire:        That's great. I now want to hear a little bit about your findings, because they're really cool. So you took two approaches to study this, and the first was looking at the astrocytes and how they become these, what you're calling reactive astrocytes, and then you look specifically at the brain endothelium. So could you maybe just summarize those two big findings for us?   Miguel Lopez-Ramirez: Yeah, so, basically by doing these studies we use trangenic animal in this case that they give us the visibility to obtain the transcripts in the astrocytes. And basically this is very important because we don't need to isolate the cells, we don't need to manipulate anything, we just took all the ribosomes that were basically capturing the mRNAs and we profile those RNAs that are specifically expressed in the astrocytes.   By doing this, we actually went into looking at in depth the transcripts that were altered in the animals that developed the disease, in this case the cerebral cavernous malformation disease, and what we look at is multiple genes that were changing. Many of them were already described in our previous work, which were associated with hypoxia and angiogenesis. But what we found in this work is that now there were a lot of genes associated with inflammation and coagulation actually, which were not identified before.   What we notice is that now these astrocytes, during the initial phase of the vascular malformation, may play a more important role in angiogenesis or the degradation of the vessels. Later during the stage of the malformation, they play a more important role in the thrombosis, in the inflammation, and recruitment of leukocyte   That was a great advantage in this work by using this approach and looking in detail, these astrocytes. Also, we identified there were very important signature in these astrocytes that we refer as a reactive astrocytes with neuroinflammatory properties. In the same animals, basically, not in the same animal, but in the same basically the experimental approach, we isolated brain vasculature. And by doing the same, we actually identified not only the astrocyte but also the endothelium was quite a different pattern that we were not seeing before. And this pattern was also associated with inflammation, hypoxia and coagulation pathways.   That lead us to go into more detail of what was relevant in this vascular malformations. And one additional part that in the paper this is novel and very impactful, is that we identify inflammasome as a one important component, and particularly in those lesions that are multi-cavernous.   Now we have two different approaches. One, we see this temporality in which the lesions forms different patterns in which the initial phase maybe is more aneugenic, but as they become more progressive in chronocytes, inflammation and hypoxy pathways are more relevant for the recruitment of the inflammatory cells and also the precipitation of immunothrombosis.   But also what we notice is that inflammasome in endothelial and in the leukocytes may play an important role in the multi-cavernous formation, and that's something that we are looking in more detail, if therapeutics or also interventions in these pathways could ameliorate the transition of phases between single lesions into a more aggressive lesions.   Cindy St. Hilaire:        That's kind of one of the follow up questions I was thinking about too is, from looking at the data that you have, obviously to get a CCM, there's a physical issue in the vessel, right? It's not formed properly. Does that form influence the activation of the astrocyte, and then the astrocytes, I guess, secrete inflammatory factors, target more inflammation in the vessel? Or is there something coming from the CCM initially that's then activating the astrocyte? It's kind of a chicken and the egg question, but do you have a sense of secondary to the malformation, what is the initial trigger?   Miguel Lopez-Ramirez: The malformations in our model, and this is important in our model, definitely start by producing changes in the brain endothelial. And as you mention it, these endothelium start secreting molecules that actually directly affect the neighboring cells.   One of the first neighboring cells that at least we have identified to be affected is the astrocytes, but clearly could be also pericytes or other cells that are in the neurovascular unit or form part of the neurovascular unit. But what we have seen now is that this interaction gets extended into more robust interactions that what you were referring as the CaLM interactions.   Definitely I think during the vascular malformations maybe is the discommunication that we identify already few of those very strong iteration that is part of the follow up manuscript that we have. But also it could be the blood brain barrier breakdown and other changes in the endothelium could also trigger the activation of the astrocytes and brain cells.   Cindy St. Hilaire:        What does your data suggest about potential future therapies of CCM? I know you have a really intriguing statement or data that showed targeting NF-kappa B isn't likely going to be a good therapeutic strategy. So maybe tell us just a little bit about that, but also, what does that imply, perhaps, of what a therapeutic strategy could be?   Bliss Nelson:                Originally we did think that the inhibition of NF-kappa B would cause an improvement potentially downstream of the CCMs. And unexpectedly, to our surprise, the partial or total loss of the brain endothelial NF-kappa B activity in the chronic model of the mice, it didn't prevent or cause any improvement in the lesion genesis or neuroinflammation, but instead it resulted in a trend to increase the number of lesions and immunothrombosis, suggesting that the inhibition of it is actually worsening the disease and shouldn't be used as a target for therapeutical approaches.   Miguel Lopez-Ramirez: Yes, particularly that's also part of the work that we have ongoing in which NF-kappa B may also play a role in preventing the further increase of inflammation. So that is something that it can also be very important. And this is very particular for certain cell types. It's very little known what the NF-kappa B actually is doing in the brain endothelial during malformations or inflammation per se. So now it's telling us that this is something that we have to consider for the future.   Also, our future therapeutics of what we propose are two main therapeutic targets. One is the harmful hypoxia pathway, which involves activation, again, of the population pathway inflammation, but also the inflammasomes. So these two venues are part of our ongoing work in trying to see if we have a way to target with a more safe and basically efficient way this inflammation.   However, knowing the mechanisms of how these neuroinflammation take place is what is the key for understanding the disease. And maybe even that inflammatory and inflammatory compounds may not be the direct therapeutic approach, but by understanding these mechanisms, we may come with  new approaches that will help for safe and effective therapies.   Cindy St. Hilaire:        What was the most challenging part of this study? I'm going to guess it has something to do with the mice, but in terms of collecting the data or figure out what's going on, what was the most challenging?   Bliss Nelson:                To this, I'd like to say that I think our team is very strong. We work very well together, so I think even the most challenging part of completing this paper wasn't so challenging because we have a really strong support system among ourselves, with Miguel as a great mentor. And then there's also two postdocs in the lab who are also first authors that contributed a lot to it.   Cindy St. Hilaire:        Great. Well, I just want to commend both of you on an amazing, beautiful story. I loved a lot of the imaging in it, really well done, very technically challenging, I think, pulling out these specific sets of cells and investigating what's happening in them. Really well done study. And Bliss, as an undergraduate student, quite an impressive amount of work. And I congratulate both you and your team on such a wonderful story.   Bliss Nelson:                Thank you very much.   Miguel Lopez-Ramirez: Thank you for Bliss and also Elios and Edo and Katrine, who all contributed      enormously to the completion of this project.   Cindy St. Hilaire:        It always takes a team.   Miguel Lopez-Ramirez: Yes.   Cindy St. Hilaire:        Great. Well, thank you so much, and I can't wait to see what's next for this story.   Cindy St. Hilaire:        That's it for the highlights from October 28th and November 11th issues of Circulation Research. Thank you so much for listening. Please check out the Circ Res Facebook page and follow us on Twitter and Instagram with the handle @circres and #discovercircres. Thank you to our guests, Dr Miguel Lopez-Ramirez and Bliss Nelson. This podcast is produced by Ashara Retniyaka, edited by Melissa Stoner, and supported by the editorial team of Circulation Research. Some of the copy text for our highlighted articles is provided by Ruth Williams. I'm your host, Dr Cindy St. Hilaire, and this is Discover CircRes, you're on the go source for the most exciting discoveries in basic cardiovascular research. This program is copyright of the American Heart Association 2022. The opinions expressed by speakers in this podcast are their own and not necessarily those of the editors or of the American Heart Association. For more information, please visit ahagenerals.org.

Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2022.11.04.515167v1?rss=1 Authors: Mann, J. P., Tabara, L., Alvarez-Guaita, A., Dong, L., Haider, A., Lim, K., Tandon, P., Minchin, J. E., O'Rahilly, S., Patel, S., Fazakerley, D. J., Prudent, J., Semple, R. K., Savage, D. B. Abstract: Objective: A biallelic missense mutation in mitofusin 2 (MFN2) causes multiple symmetric lipomatosis and partial lipodystrophy, implicating disruption of mitochondrial fusion or interaction with other organelles in adipocyte differentiation, growth and/or survival. In this study, we aimed to document the impact of loss of mitofusin 1 (Mfn1) or 2 (Mfn2) on adipogenesis in cultured cells. Methods: We characterised adipocyte differentiation of wildtype (WT), Mfn1-/- and Mfn2-/- mouse embryonic fibroblasts (MEFs) and 3T3-L1 preadipocytes in which Mfn1 or 2 levels were reduced using siRNA. Results: Mfn1-/- MEFs displayed striking fragmentation of the mitochondrial network, with surprisingly enhanced propensity to differentiate into adipocytes, as assessed by lipid accumulation, expression of adipocyte markers (Plin1, Fabp4, Glut4, Adipoq), and insulin-stimulated glucose uptake. RNA sequencing revealed a corresponding pro-adipogenic transcriptional profile including Pparg upregulation. Mfn2-/- MEFs also had a disrupted mitochondrial morphology, but in contrast to Mfn1-/- MEFs they showed reduced expression of adipocyte markers and no increase in insulin-stimulated glucose uptake. Mfn1 and Mfn2 siRNA mediated knockdown studies in 3T3-L1 adipocytes generally replicated these findings. Conclusions: Loss of Mfn1 but not Mfn2 in cultured pre-adipocyte models is pro-adipogenic. This suggests distinct, non-redundant roles for the two mitofusin orthologues in adipocyte differentiation. Copy rights belong to original authors. Visit the link for more info Podcast created by Paper Player, LLC

Everyone wants to find the right diet and exercise regime that works for them. But with all the choices available to us, finding the right fit can be a long journey full of shots in the dark and a lack of real data. David Krantz is changing that by offering personalized health coaching that looks at each client's gene expression, and then building a diet and exercise program that is a right fit for each person.David specializes in coaching around epigenetics. This allows him to coach people on nutrigenomics - the study of linking epigenetic expression to particular foods and behaviours.We all have a particular set of expressed gene codes, and this regulates what foods work well in our bodies, how well we respond to exercise, and a whole host of other things. Knowing how your genes are expressed allows you (with the right advisor) to make decisions on how to live, based on what works well for your unique body.On this episode, we discuss: What epigenetic coaching does. The old way of discovering what's healthy for you. The new way of tailoring diet and exercise to your genetic expression. Why a Ketogenic diet may not be a good fit for you. The most direct route to changing how your body loses weight. Marrying intuition and data together = power. How good data can empower you to move forward and take bold action. Concerns: Genetic testing, privacy, and big brother having your genetic information. Genetics and specific foods: fats, nuts, and more. The PPARG gene and mitochondria response to cold therapy. The function of mitochondria - the power-plant of the cells in your body. Mitochondrial response to infra red light. Cold exposure and how it affects sleep quality. Genes in my chart that affect Dopamine and my appetite for dopamine rushes. Why some people absolutely hate cold exposure. Addiction and which genes contribute to addictive tendencies. Supplements and substances that can contribute to balancing or resetting receptor systems in the brain. Ibogane and Ayahuasca for addiction treatment. How your genetic variants can predict your response to Cannabis. The the important balance of mind and body - therapy and diet/exercise. The importance of Purpose in leading a life of meaning. One take-home message from this podcast with David is this:March to the beat of your own drum. Every body is different. Listen to your own body and learn what you need.David's website is full of great content, and he offers multiple tiers of coaching for short term and long term goals. David-Krantz.comBook a free 30 minute call with David here.See omnystudio.com/listener for privacy information.

With so much information out there, it can be extremely difficult to find the nutrition plan that will allow you to achieve optimal health and the best physical results. In our constant quest for wellbeing, more energy and longer life, finding the plan that works for us as individuals can be a tricky task. In this episode, Angela discusses personalised nutrition and whether or not there’s a single nutritional protocol that can positively benefit everyone. KEY TAKEAWAYS Human beings share many of the same genes, but the small variants in our genetic make-up can radically alter the way we process and generate energy from proteins, fats and carbohydrates. Our capacity for digesting different types of food is partly dependent on the types of foods our ancestors ate. One way of determining which dietary course is right for us is to figure out which ancestral strain we belong to, thereby learning exactly how our bodies process different food types. We can find this information out by looking at our own DNA. After testing her own genetics, Angela discovered that she was particularly sensitive to carbohydrates, and was struggling with PCOS and insulin resistance. Both of her parents’ sides of the family had a strong history of Type II Diabetes. After being told that these conditions might affect her ability to have children, Angela began to research ways of controlling PCOS through nutrition. The beta adreno-receptor gene variants ADRB2 27 and 16 are vitally important in unlocking fat cells and allowing fat to be burned for energy. Knowing your own variant is vital in understanding how your body will react to carbohydrate intake and staying lean and healthy. If you carry a certain variant of ADRB2 27, and your aim is to shed body fat through exercise, then you may need to stimulate this gene more and so will benefit greatly from beta-receptor stimulation before you exercise. This can be done by taking caffeine. Understanding how quickly you metabolise caffeine can help you fine-tune things further. The FTO gene (or “Fatso” gene) is a protein prevalent in the body that’s associated with obesity in adults and children, and acts as a nutrient sensor that impacts hunger and the amount of food we need before we are satisfied. Scientists have found that those with variants of the FTO gene often have a higher Body Mass Index (BMI). PPARG has been called the “Thrifty Gene” and was named so for its use as a fat-storer. In past times, this gene would have enabled the build-up of body fat to allow humans to survive winters. Now that food is abundant, too much activation of PPARG can cause weight gain and increase the risks of heart disease and stroke.  Time restricted eating is an incredibly powerful way of lowering inflammation and enhancing body composition. It also acts as a fantastic kickstarter to losing body fat.  Angela’s top five nutritional practices for achieving a healthy body and maintaining it are:  Ruthlessly remove all highly processed foods from your diet.  Move, move, move! Prioritise your sleep Use time-restricted eating to restrict your window of eating to a maximum of twelve hours per day Test your DNA (you only need to do this once!) and test your key blood bio-markers and your gut annually. BEST MOMENTS ‘This is a complex process that happens in our cells over a billion times per second’ ’Not everyone is as sensitive to carbs as another person’ ‘If you’re someone who’s hungry all the time, it could be that the FTO gene is playing a part here’ ‘It’s the expression of our genes that’s important’ ‘Processed foods are driving the increase in heart disease and weight gain that we’re currently seeing’ ‘The sedentary lifestyle has been dubbed the new smoking for a reason’ VALUABLE RESOURCES   The High Performance Health Podcast – Omny  For more information on DNA testing and assessing your epigenetic expression, go to bit.ly/personalisedhealth For ways to optimise your workspace, go to bit.ly/workspacehacks Why We Sleep by Matthew Walker: https://amzn.to/2XDfsUB   ABOUT THE HOST Angela Foster Angela is a Nutritionist, Health and Performance Coach. She is also the Founder and CEO of My DNA Edge, an Exclusive Private Membership Site giving individuals the tools and biohacks needed to optimise their genetic expression for optimal health and performance. After recovering from a serious illness in 2014, Angela left the world of Corporate Law with a single mission in mind: To inspire and educate others to live an energetic, healthful and limitless life. Angela believes that we can truly have it all and has spent the last 5 years researching the habits and routines of high performers, uncovering age old secrets, time honoured holistic practices and modern science to create a blueprint for Optimal Human Performance. CONTACT DETAILS Instagram Facebook LinkedIn High Performance Health FB Group

Apply for My DNA Coach's Academy by clicking here - This week we look at PPARG, a gene that appears in both our carbohydrate and fat sensitivity panels within our diet report. This gene creates a protein known as peroxisome proliferator-activated receptor gamma, which plays a role in the formation of fat cells, as well as the use of fats and carbohydrates as a source of energy. Studies Referenced in the Episode: https://academic.oup.com/hmg/article/12/22/2923/606582/Interaction-between-a-peroxisome-proliferator   PPARG Genotype Effect CC Individuals with the CC genotype are likely to be more sensitive to the negative effects of fats and refined carbohydrates within the diet. As such, they should consume wholegrain carbohydrates, as well as fruits and vegetables, alongside a moderate intake of fats – with a focus on poly- and mono-unsaturated fatty acids. CT/TT Neither genotype is associated with an increased sensitivity to refined carbohydrates or saturated fats.  

On the show today we have Kurt Johnsen, the vision keeper and co-founder of Simplified Genetics. Kurt is passionate about positively impacting the lives of people around the world. In fact, as you’ll hear in this episode, one of his strongest motivations is to do good and give back. In addition to his work at Simplified Genetics, Kurt is the senior columnist for Yoga Digest and the official yoga trainer of the Dallas Cowboys cheerleaders. Find Out More About Kurt Here: Kurt Johnsen on LinkedInKurt Johnsen on Facebook@kurtjohnsen on TwitterSimplified Genetics In This Episode: [01:23] - Kurt talks a bit about himself and explains how he got involved in genetics. He then goes into depth about the kind of testing his company does and explain why it’s valuable compared to tests by other companies. [05:40] - Kurt goes into the dieting side of things, explaining that his tests reveals fat and glucose sensitivity. [07:43] - Is a vegan diet healthy for some people based on their genes? [08:58] - Stephen talks about a diet he’s recently heard about that involves simply tracking your macros without paying attention to the quality of the food. Kurt responds by saying he believes we need to eat things that get energy from the sun. [11:06] - Kurt talks about the impact that his testing has had, revealing that lots of people have lost 70-100 pounds after their testing. He then goes into more depth about eating and exercise. [13:54] - Stephan asks about calorie counting, then talks about a fitness tracker called Healbe GoBe Health Tracker. [15:10] - We learn why Kurt is against calorie counting, what he recommends instead, and what he believes is the reason that we’re suffering from overeating (which has to do with the fact that just one or two hundred years ago, this abundance of food would have been unimaginable). [19:30] - Does Kurt think there’s any validity to eating for your blood type? [20:58] - For listeners unfamiliar with the term, Kurt explains what Ayurvedic medicine is. He and Stephan then briefly talk about mesomorph, ectomorph, and endomorph body types. [22:36] - Kurt talks about exercise, adrenergic receptors and positions, and the fact that your body can’t tell what kind of exercise you’re doing. He then explains that there are 162 possible variations on the genetic report (based on four genes adding up to 81 combinations multiplied by two to account for gender). [27:19] - Kurt offers the example of his wife, a yoga teacher who had struggled with her body competition. He explains why his wife’s body reacted very differently than her sister’s to the same exercises. [29:28] - We hear more about how different genetic types can respond differently to certain kinds of exercise, and that it’s not as simple as “calories in, calories out.” [30:50] - How does the concept of fast twitch muscles versus slow twitch muscles fit into this equation? [32:23] - Stephen offers his specific report as an example. He’s a 70-30, meaning he should do 70% low intensity and 30% high intensity exercise. What would happen if he’s exercising in different proportions? [35:29] - Kurt talks about the PPARG, which his wife compares to an old friend who holds a grudge when you ignore them for a while. [37:46] - Stephan and Kurt discuss their relative body fat percentages. Kurt reveals how much of his body fat percentage he has dropped. [40:48] - Kurt returns to the topic of his wife’s weight struggles and reveals how much exercising for her genetic type has helped her with this. He then contrasts this to the proportions of exercise needed by people with the genetic type that he and Stephan share. Next, he talks about why high-intensity exercise often seems to stop working for women after a month or two. [43:43] - Stephan brings up the bioDensity machine, invented by John Jaquish. Kurt is unfamiliar with it, so Stephan expands on it, explaining that Tony Robbins is a fan. Stephan then explains why the machine is so expensive. [46:37] - Developing density with intensity makes sense, Kurt says, and weight training is important. [48:38] - We move from Simply Fit to Kurt’s other product, Simply Safe. Kurt explains that Simply Safe looks at the infamous APOE gene. This gene is responsible for “the response to brain insults” such as concussions or heat stroke. He goes into depth about how this gene impacts susceptibility to concussions, and explains that it’s also linked to Alzheimer’s. [52:44] - Kurt explains the different sports that he would have encouraged his son to get involved in based on his APOE type. He then describes his work with pro hockey players, and reveals why they’ve had to shelf Simply Safe for now. [55:05] - Kurt talks about a study by Dr. Daniel Amen as it relates to the APOE gene in different populations. [57:17] - Stephan doesn’t believe that the FDA has the consumer’s best interest at heart, and explains how this relates to 23andMe. Kurt agrees, stating that it’s our right to have this information that is basically the body’s instruction manual. [59:40] - Kurt doesn’t have a solution, but he explains some rights that he believes people have when it comes to genetics. He then expands on this to talk about a societal victim mentality and the importance of taking control of your life. [63:01] - Stephan runs through a few points for listeners. He then reveals how listeners can get 10% off the Simply Fit test. Links and Resources: Kurt Johnsen on LinkedInKurt Johnsen on Facebook@kurtjohnsen on TwitterSimplified GeneticsYoga DigestDallas Cowboys cheerleadersSimply FitAmerican Power YogaMyFitnessPalHealbe Gobe Health TrackerAdrenergic receptorsAtkins dietCrossFitAyurvedic medicineMesomorph, ectomorph, and endomorph body typesCatecholaminesADRB3 PPARG ACTN3 Fast twitch muscles versus slow twitch musclesThe bioDensity machineJohn Jaquish on the Optimized GeekTony RobbinsAPOE Dr. Daniel Amen on the Optimized Geek23andMe Change Your Brain, Change Your Life by Dr. Daniel AmenFreakonomics by Steven Levitt and Stephen Dubner

Thu, 17 Feb 2011 12:00:00 +0100 https://edoc.ub.uni-muenchen.de/12784/ https://edoc.ub.uni-muenchen.de/12784/1/Markus_Christian.pdf Markus, Christian

Apart from its regulatory function in lipid and glucose metabolism, peroxisome proliferator-activated receptor (PPAR)γ has impact on the regulation of inflammation and bone metabolism. The aim of the study was to investigate the association of five polymorphisms (rs10865710, rs2067819, rs3892175, rs1801282, rs3856806) within the PPARG gene with chronic periodontitis. The study population comprised 402 periodontitis patients and 793 healthy individuals. Genotyping of the PPARG gene polymorphisms was performed by PCR and melting curve analysis. Comparison of frequency distribution of genotypes between individuals with periodontal disease and healthy controls for the polymorphism rs3856806 showed a P-value of 0.04 but failed to reach significance after correction for multiple testing (P  0.90). A 3-site analysis (rs2067819-rs1801282-rs3856860) revealed five haplotypes with a frequency of ≥1% among cases and controls. Following adjustment for age, gender and smoking, none of the haplotypes was significantly different between periodontitis and healthy controls after Bonferroni correction. This study could not show a significant association between PPARG gene variants and chronic periodontitis.