Mind & Matter

• Genetics & Neurobiology of Obesity: Hypothalamus, Leptin, Gut Hormones, Weight Loss Drugs | Giles Yeo | 222

  Send us a textShort Summary: The science of obesity and appetite regulation, blending genetics and neurobiology with practical insightsAbout the guest: Giles Yeo, PhD is a professor of molecular neuroendocrinology at the University of Cambridge. He leads a lab studying obesity and appetite regulation.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.Episode Summary: Nick interviews Dr. Giles Yeo about the genetics and neurobiology of obesity, starting with the discovery of leptin in the obese mouse model, detailing its role in appetite regulation via the hypothalamus, and discussing GLP-1 drugs like Ozempic for weight loss. It delves into how genetic factors, like the leptin-melanocortin pathway, influence hunger, the heritability of body weight, and societal factors driving the obesity epidemic, emphasizing the interplay of biology and environment.Key Takeaways:Leptin, discovered through the obese mouse, signals fat levels to the brain, but its absence causes severe obesity and infertility, as seen in rare human mutations.The hypothalamus, a key brain region, senses hormones like leptin and GLP-1, balancing hunger and satiety through POMC (anorexigenic) and AgRP (orexigenic) neurons.Body weight heritability is 40-70% at the population level, but this does not mean that 40-70% of someone’s body fat composition is due to genetic factors outside human control. Dr. Yeo unpacks how to think about it.GLP-1 drugs (e.g., Ozempic) mimic gut hormones to reduce appetite, offering some people 15-25% weight loss, but require long-term safety monitoring.According to Dr. Yeo, obesity reflects energy imbalance, but nutritional density matters more than calorie counting for health, and societal changes are needed to prevent it.Related episode:M&M #132: Obesity Epidemic, Diet, Metabolism, Saturated Fat vs. PUFAs, Energy Expenditure, Weight Gain & FeediSupport the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Use code MIND for 10% off. Readwise: Organize and share what you read. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off. For all the ways you can support my efforts

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• Regenerative Energy & the Light Inside You | Jack Kruse | 221

  Send us a textShort Summary: A mind-bending dive into evolutionary biology and health through a biophysicist’s lens, with Dr. Jack Kruse delivering provocative insights about biology, medicine, and health.About the guest: Jack Kruse, MD, is a neurosurgeon known for integrating biophysics into medicine. He challenges conventional biochemistry with his “leptin prescription” and decentralized health approach.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.Episode Summary: Dr. Jack Kruse joins host Nick Jikomes to explore the Great Oxygenation Event’s role in shaping life, linking it to modern health via biophysics over biochemistry. They discuss oxygen’s impact on metabolism, the significance of deuterium-depleted water, and sunlight’s influence on the leptin-melanocortin pathway. Kruse shares his dramatic weight loss journey using sunlight and cold therapy, critiques modern tech-driven obesity, and unveils a controversial history of SV40 in vaccines, tying it to cancer spikes.Key Takeaways:The Great Oxygenation Event (2.1-2.4 billion years ago) drove life’s shift to oxygen-based metabolism, with cyanobacteria as key players.Kruse argues biophysics, not biochemistry, explains evolution, spotlighting light as life’s fundamental driver.Deuterium-depleted water is important for enabling our cells and mitochondria to use energy from the TCA cycle without “shocking” the body.Sunlight exposure boosts nitric oxide, reducing food needs via the leptin pathway, challenging diet norms.Kruse lost 133 pounds in 11 months using sunlight and cold therapy, inspiring his “leptin prescription.”He links obesity to indoor tech lifestyles, disrupting heme proteins and mitochondrial function.SV40, a virus in 1950s polio vaccines, may connect to cancer rises, a story Kruse says was buried by centralized science.Related episode:M&M #196: Vaccine Contamination & Fiat Science Support the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Use code MIND for 10% off. Readwise: Organize and share what you read. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off. For all the ways you can support my efforts

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• Cell Death, Oxidative Stress, PUFAs & Antioxidants | Pamela Maher | 220

  Send us a textShort Summary: A deep dive into the science of oxidative stress, antioxidants, aging, and neurodegenerative diseases like Alzheimer’s.About the guest: Pamela Maher, PhD is a professor at the Salk Institute in San Diego, California, with a focus on neurodegenerative diseases, oxidative stress, and antioxidants.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.Episode Summary: Dr. Pamela Maher discusses her research on cell death mechanisms, including apoptosis and ferroptosis, and their roles in health and disease. They discuss how oxidative stress from reactive oxygen species can damage cells, the body’s antioxidant defenses like glutathione and studies on natural compounds—fisetin, curcumin, and cannabinol (CBN)—that may protect against brain cell loss. The conversation covers CBN’s mitochondrial benefits in aging mouse models and broader risk factors for dementia, like obesity and hearing loss, emphasizing early intervention.Key Takeaways:Apoptosis is a controlled cell death process vital for development, while ferroptosis, linked to oxidative stress and iron, causes cells to burst and is tied to diseases like Alzheimer’s.Oxidative stress arises when reactive oxygen species overwhelm antioxidants, damaging DNA, proteins, and cell membranes, especially polyunsaturated fats.Glutathione, a key antioxidant, relies on cysteine and declines with age, but supplements like N-acetylcysteine might help, though tolerability varies.Cannabinol (CBN), a THC byproduct, protects mitochondria and improves memory in aging mice, hinting at therapeutic potential beyond cannabinoid receptors.Middle-age risk factors like visceral obesity, type 2 diabetes, and hearing loss significantly increase dementia risk, but hearing aids can reduce it.Related episode:M&M #165: PUFAs in Brain Health & Disease, Dietary Fats, Brain Lipids, Nutrition | Richard Bazinet*Not medical aSupport the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Use code MIND for 10% off. Readwise: Organize and share what you read. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off. For all the ways you can support my efforts

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• Shamanism, Human Culture & the Evolution of Religion | Manvir Singh | 219

  Send us a textShort Summary: A detailed examination of shamanism with anthropologist Manvir Singh, blending evolutionary theory and vivid storytelling.About the guest: Manvir Singh, PhD is an anthropologist at the University of California, Davis. His new book, "Shamanism: The Timeless Religion," comes out on May 25, 2025.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.Episode Summary: Dr. Manvir Singh discusses shamanism’s role as a universal human practice, exploring its roots in cultural evolution, cognitive tendencies, and persistence across history and modern society. They discuss how shamans use altered states to address uncertainty—like healing or divination—while examining shamanism’s interplay with centralized religion, its psychological benefits, and parallels in today’s world, from tech gurus to medical placebos.Key Takeaways:Shamanism is a widespread cultural practice involving specialists who enter altered states to engage with unseen forces, often for healing or managing uncertainty.It’s not an archaic precursor to modern religion but a recurring expression of spiritual beliefs & practices, competing with other forms.Techniques vary widely—dance, music, psychedelics—but only about half of shamans historically used psychoactive substances.Modern parallels include tech CEOs and money managers who project exceptionalism to influence others, echoing shamanic charisma without trance.Open-label placebos (where patients know it’s fake) still work, suggesting rituals alone can trigger healing, much like shamanic practices.Singh sees shamanism as a cognitive technology, not inherently good or bad, shaping how we cope with chaos across cultures and time.Related episode:M&M #86: Shamanism, Psychedelics, Social Behavior, Religion & Evolution of Human Culture | Michael Winkelman*Not medical advice.Support the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Use code MIND for 10% off. Readwise: Organize and share what you read. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off. For all the ways you can support my efforts

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• Chemical Exposures, Neurodegenerative Disease & Exposomics | Gary Miller | 218

  Send us a textShort Summary: How environmental chemical exposures affect neurodegenerative disease and health.About the guest: Gary Miller, PhD is a Professor of Environmental Health Sciences at Columbia University. His research bridges pharmacology, toxicology, and neuroscience to explore neurodegeneration, particularly Parkinson’s and Alzheimer’s diseases.Note: Podcast episodes are fully available to paid subscribers on the M&M Substack and everyone on YouTube. Partial versions are available elsewhere. Full transcript and other information on Substack.Episode Summary: Dr. Gary Miller talks about neurodegenerative diseases like Parkinson’s and Alzheimer’s, exploring their age-driven nature, early detection challenges, and environmental risk factors such as pesticide exposure and head trauma. They discuss the emerging field of exposomics—studying lifetime chemical exposures—and its potential to uncover links between pollutants, diet, and disease, while highlighting protective factors like caffeine and nicotine, and the role of technology in advancing prevention and treatment.Key Takeaways:Neurodegenerative diseases like Parkinson’s & Alzheimer’s worsen with age, but early intervention could slow progression & improve quality of life.Parkinson’s symptoms often appear after significant dopamine neuron loss, but subtle signs like handwriting changes or gait issues might be detectable earlier.Environmental factors, including pesticides & air pollution, increase neurodegeneration risk, while caffeine and nicotine surprisingly lower Parkinson’s incidence.The exposome—total lifetime exposure to chemicals—offers a new lens to study health, revealing how pollutants & diet interact with our biology.Ultra-processed foods & common chemicals like PFAS (in packaging) raise exposure levels, but simple steps like air filters or less processed diets can help reduce risks.Related episode:M&M #145: Epigenetics, Hormones, Endocrine Disruptors, Microplastics, Xenoestrogens, Obesogens & Obesity, Inheritance of ASupport the showAll episodes, show notes, transcripts, etc. at the M&M Substack Affiliates: Lumen device to optimize your metabolism for weight loss or athletic performance. Use code MIND for 10% off. Readwise: Organize and share what you read. Athletic Greens: Comprehensive & convenient daily nutrition. Free 1-year supply of vitamin D with purchase. KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription. MASA Chips—delicious tortilla chips made from organic corn and grass-fed beef tallow. No seed oils or artificial ingredients. Use code MIND for 20% off. For all the ways you can support my efforts

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