Synapse Energetics & Fat Metabolism in the Brain | Timothy Ryan | 241

Send us a text How brain synapses work and fuel themselves with fat. Episode Summary: Dr. Timothy Ryan talks about the high energy costs of synapses, the role of mitochondria and glycolysis, and challenge the long-held view that the brain relies solely on glucose by discussing new evidence that neurons burn fats from lipid droplets for fuel, especially during activity. The talk touches on metabolic flexibility, links to epilepsy treatments like ketogenic diets, neurodegenerative diseases, and future research on brain energy sources. About the guest: Timothy Ryan, PhD is a professor of biochemistry at Cornell University. His research focuses on the molecular mechanisms of synaptic transmission, particularly vesicle recycling and the bioenergetics that power neural communication.  Discussion Points:Synapses are tiny structures with ~100 vesicles per site (on average), converting electrical signals to chemical ones.Brain tissue is energy-hungry due to trillions of synapses (in humans), relying on local mitochondria (present in only ~half of synapses) and glycolysis.Vesicles use proton pumps and transporters to concentrate neurotransmitters, requiring ATP to maintain gradients.Neurons are metabolically fragile; cutting fuel supply quickly impairs synapses.Dogma held brains don"t burn fats, but new work shows neurons form lipid droplets (fat stores) that are invisible because constantly used for energy via beta-oxidation.Silencing neurons builds lipid droplets like resting muscle; activity speeds their breakdown, indicating demand-driven fat use.Inhibiting neuron-specific fat-processing enzymes accumulates droplets and induces torpor (hibernation-like state) in animals, signaling metabolic stress.Ketogenic diets aid epilepsy by shifting to ketones; fats may explain this, with potential ties to aging and neurodegeneration like Alzheimer"s.Brain may be a "hybrid" fuel user (glucose + fats), with open questions on fat sources and roles in cognition or disease protection. Related episode:M&M 158: Ketosis & Ketogenic Diet: Brain & Mental Health, Metabolism, Diet & Exercise, Cancer, Diabetes | Dominic D"Agostino *Not medical advice. Support the show All episodes, show notes, transcripts, and more at the M&M Substack Affiliates: KetoCitra—Ketone body BHB + potassium, calcium & magnesium, formulated with kidney health in mind. Use code MIND20 for 20% off any subscription (cancel anytime) Lumen device to optimize your metabolism for weight loss or athletic performance. Code MIND for 10% off Readwise: Organize and share what you read. 60 days FREE through link SiPhox Health—Affordable at-home blood testing. Key health markers, visualized & explained. Code TRIKOMES for a 20% discount. MASA Chips—delicious tortilla chips made from organic corn & grass-fed beef tallow. No seed oils or artificial ingredients. Code MIND for 20% off For all the ways you can support my efforts