Mind & Matter

Amita Sehgal, neuroscientist and chronobiologist studying sleep with fruit fly genetics, explores why animals sleep. She discusses how waking creates oxidized lipids that move from neurons to glia and are cleared during sleep. Immune-like cells dock to the brain to remove lipid waste. Topics include mitochondrial protection, peroxisomes, lipid transfer via apolipoproteins, and differences between sickness and normal sleep.

Flynn McGuire, MD — a PM&R physician and researcher focused on neurologic recovery and musculoskeletal care. He discusses why peptides like BPC-157 and TB-500 rose in popularity. Short explanations of peptide biology, preclinical evidence for tissue repair, mechanisms like angiogenesis, stacking practices, major gaps in human trials, safety and sourcing risks.

Send us Fan MailBiology of obesity resistance and factors influencing weight gain in humans and animals.TOPICS DISCUSSED:Historical views on obesity: In some cultures, like northern Africa or Stone Age societies, high body fat signaled status or attractiveness due to food scarcity, unlike today’s focus on leanness amid calorie abundance.Energy balance components: Metabolizable energy (95% absorption on average, but varying 1-11%) and unabsorbed nutrients excreted as waste significantly influence weight.Obesity resistance in animals: Inbred mouse strains show wide variation in weight gain on high-fat diets, often somewhat uncoupled from overeating, suggesting roles for feed efficiency, energy expenditure, or waste rather than intake alone.Genetic & twin studies: Monozygotic twins overfed 1,000 extra calories daily vary widely in weight gain (4-13 kg), indicating genetic influences, while mouse litter size affects lifelong obesity propensity via early-life programming.Bloodborne factors & hormones: Parabiosis studies led to leptin’s discovery for defending against weight loss, but evolutionary logic suggests systems also prevent excess gain, though modern environments may weaken this.Human thinness research: Constitutionally thin people snack more, move less, yet have better cardiometabolic health, but we don’t yet understand why.GLP-1 drugs & future directions: These slow gut transit and suppress appetite, but obesity’s root causes remain unclear; emerging thinness studies could inform prevention beyond drugs.ABOUT THE GUEST: Jens Lund, PhD is a postdoctoral researcher at the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research.RELATED EPISODE:M&M 132 | Obesity Epidemic, Diet, Metabolism, Saturated Fat vs. PUFAs, Energy Expenditure, Weight Gain & Feeding Behavior | John SpeakmanSupport the showHealth Products by M&M Partners:SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.Lumen device: Optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off.AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models.Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app.KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime)For all the ways you can support my efforts

Douglas Wallace, a mitochondrial geneticist and evolutionary biologist leading CHOP’s mitochondrial center, walks through mitochondria’s origins and their role in human evolution. He discusses maternal inheritance, haplogroups and climate adaptation, heteroplasmy and aging, bioenergetics in disease, ketogenic diets, cancer metabolism, and how modern mismatches affect metabolic health.

Rebecca Haeusler, associate professor at Columbia studying insulin signaling, bile acids and metabolic liver disease. She explains how bile acids handle cholesterol and fat digestion. They discuss bile production and regulation, links between bile acids and insulin resistance or diabetes, effects of gallbladder removal and bariatric surgery, and ongoing lab work on bile transport and liver inflammation.

Joseph Bass, Chief of Endocrinology and metabolism researcher who links circadian clock genes to obesity and diabetes. He explains how light and feeding set brain and peripheral clocks. He explores how mistimed eating, shift work, and night feeding disrupt metabolism. He discusses clock gene effects on insulin and weight, and how timing influences drug and study outcomes.

Send us Fan MailGene regulation through RNAs, the neurobiology of opioid addiction, and how psychedelics affect drug-seeking by modulating inflammation and plasticity. Not medical advice.TOPICS DISCUSSED:Gene regulation basics: DNA transcribes to RNAs, including non-coding types like microRNAs that inhibit mRNA translation into proteins, influencing up to 60% of the proteome.Non-coding RNAs in neuroplasticity: MicroRNAs and circular RNAs regulate synaptic changes, with activity-induced ones like miR-485-5p linked to rapid responses in drug cue memory and addiction reinforcement.Opioid addiction models: Rats self-administer heroin or fentanyl via levers, showing compulsive seeking; fentanyl’s higher potency drives faster learning but similar long-term effects to heroin when doses are equated.Differences between opioids: Heroin and fentanyl both activate mu-opioid receptors for euphoria and dopamine release, but fentanyl lingers longer; no major behavioral differences in seeking once potency is matched.Psilocybin’s effects on addiction: A single psilocybin dose post-abstinence reduces heroin-seeking in rats by dampening neuroinflammation in brain regions like the nucleus accumbens and prefrontal cortex.Brain Inflammation: Opioids induce pro-inflammatory changes via cytokines like IL-17A and pathways like TNF-alpha, leading to glial activation and blood-brain barrier leaks; psilocybin counters this.MicroRNA biomarkers: Blood microRNAs reflect gene expression patterns tied to disease states, with potential to predict opioid relapse risk, treatment response, or neonatal withdrawal severity non-invasively.Future research: Ongoing work links psilocybin’s serotonin 2A activation to anti-inflammatory gene changes, plus human studies on microRNAs for personalized addiction treatments.ABOUT THE GUEST: Stephanie Daws, PhD is an associate professor at Temple University in the Center for Substance Abuse Research and Department of Neurosciences, where she researches mechanisms of drug-seeking behavior with a focus on opioids and psychedelics.RELATED EPISODE:M&M 2 | Psilocybin, LSD, Ketamine, Inflammation & Novel PsychedeliSupport the showHealth Products by M&M Partners:SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.Lumen device: Optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off.AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models.Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app.KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime)For all the ways you can support my efforts

Send us Fan MailThe biology of fat tissue, estrogen's role in metabolism and health, and how exercise interacts with these processes, especially during menopause.TOPICS DISCUSSED:Adipose tissue basics: White fat primarily stores energy in large lipid droplets, while brown fat burns fatty acids for heat via high mitochondrial density; white fat can “brown” with exercise or certain foods like capsaicin.Fat distribution & health: Subcutaneous fat (under skin) is more insulin-sensitive and less problematic than visceral fat (around organs), which links to metabolic issues; females store more subcutaneously pre-menopause, shifting to visceral post-menopause.Estrogen signaling: Estradiol binds nuclear and membrane receptors to regulate gene expression and mitochondrial function; it enhances insulin sensitivity and browning in fat cells, with receptors like ER-alpha feminizing fat distribution.Fat storage: Fat cells enlarge (hypertrophy) more than multiply in obesity, leading to hypoxia, inflammation, and insulin resistance; excess fatty acids spill to liver and muscle, worsening metabolic dysfunction.Menopause effects: Estrogen drop causes visceral fat gain, reduced energy expenditure, insulin resistance, and higher metabolic disease risk; symptoms include hot flashes and reduced exercise motivation, modeled in rodents via ovary removal.Exercise & estrogen links: Exercise boosts estrogen receptor expression and mitochondrial density in fat, mimicking estrogen’s browning effects; synergism may explain reduced exercise responsiveness post-menopause.Brain-fat connections: Estrogen in the nucleus accumbens influences exercise motivation and fat browning; manipulations there alter running behavior and adipose metabolism in rodents.ABOUT THE GUEST: Victoria Vieira-Potter, PhD leads a lab at the University of Missouri, studying how estrogen and exercise influence adipose cells.RELATED EPISODE:M&M 174 | Adipose Tissue & Body Fat: Obesity, Insulin, Leptin, Fertility, Weight Loss & GLP-1 Drugs | Sean HartigSupport the showHealth Products by M&M Partners:SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.Lumen device: Optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off.AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models.Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app.KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime)For all the ways you can support my efforts

Send a textThe brain's mysterious claustrum region, its role in cognitive flexibility, and how substances like alcohol and psychedelics affect neural circuits and behavior. Not medical advice.TOPICS DISCUSSED:Cerebral cortex structure: Described as a six-layered structure with pyramidal neurons and inhibitory interneurons; information flows between layers and regions to process sensory input and enable complex behaviors.Claustrum anatomy & connectivity: A sheet-like subcortical structure embedded in white matter, bidirectionally connected to cortical areas, especially prefrontal regions in rodents, with broader connections in primates and humans suggesting an integrative role.Claustrum function in cognition: Experiments show claustrum activation during task switches from easy to demanding modes, synchronizing cortical networks via inhibition and rebound excitation, potentially enabling flexible behavior.Mouse models in neuroscience: Mice are used for genetic tractability to manipulate and monitor specific circuits, revealing claustrum’s role in vigilance tasks but not simple ones.Alcohol’s effects on brain circuits: Chronic alcohol promotes inflexible behaviors by altering striatal interneurons and inhibitory inputs, leading to compulsive drinking despite aversive consequences.Psychedelics & brain networks: Psilocybin disrupts default mode and other networks, inhibits claustrum via serotonin 1B receptors, with effects persisting 24 hours, possibly contributing to therapeutic benefits.Evolution of claustrum: Connectivity expands from rodents to humans, shifting from cognitive-specific to broader network control, including anti-correlated states like default mode versus task-engaged.Integration of claustrum & basal ganglia: Claustrum funnels prefrontal signals to basal ganglia for action selection; alcohol may impair this, exacerbating inflexibility in addiction.ABOUT THE GUEST: Brian, PhD is a professor in the Department of Pharmacology and Physiology at the University of Maryland School of Medicine, where he leads a neuroscience lab studying brain circuits underlying flexible and inflexible behaviors using mouse models, with a focus on alcohol use disorder.Support the showHealth Products by M&M Partners:SporesMD: Premium mushrooms products (gourmet mushrooms, nootropics, research). Use code 'nickjikomes' for 20% off.Lumen device: Optimize your metabolism for weight loss or athletic performance. MINDMATTER gets you 15% off.AquaTru: Water filtration devices that remove microplastics, metals, bacteria, and more from your drinking water. Through link, $100 off AquaTru Carafe, Classic & Under Sink Units; $300 off Freestanding models.Seed Oil Scout: Find restaurants with seed oil-free options, scan food products to see what they’re hiding, with this easy-to-use mobile app.KetoCitra—Ketone body BHB + electrolytes formulated for kidney health. Use code MIND20 for 20% off any subscription (cancel anytime)For all the ways you can support my efforts

Javier Gonzalez-Maeso, PhD, a pharmacology professor studying GPCR signaling and psychedelic neurobiology. He talks about how biased agonism makes similar drugs act very differently. He explains isomers and enantiomers in MDMA and LSD. He highlights sex-specific effects of MDMA and psilocybin in animal models and implications for clinical trials and dosing.