Mind & Matter
Whether food, drugs or ideas, what you consume influences who you become. Learn directly from the best scientists & thinkers alive today about how your mind-body reacts to what you feed it.
The weekly M&M podcast features conversations with the most interesting scientists, thinkers, and technology entrepreneurs alive today.
Not medical advice.
At M&M, we are interested in trying to figure out how things work, not affirming our existing beliefs. We prefer consulting primary rather than secondary sources and independent rather than institutional voices. If we encounter uncomfortable truths or the evidence suggests unfashionable ideas may be valid, so be it.
As the host, my aim is to help you better understand how the body & mind work by curating & synthesizing information in a way that yields science-based insights that you can choose to use or disregard in your own life. Taking ownership of your health starts with taking ownership of your information diet.
I am motivated to connect the dots and distill general principles from what I learn, preferring to ask questions and play devil’s advocate to debating or incessantly pushing my own viewpoint.
My beliefs:
- Taking ownership of your health starts with taking ownership of your information diet.
- All knowledge is provisional and we must work hard to prevent ourselves from becoming attached to our favorite ideas & preferred conclusions.
- Wisdom comes from an iterative, trial-and-error process of learning and unlearning. Letting go of pre-conceived notions can be painful, but pain is information.
Sometimes modern discoveries teach us we must unlearn received wisdom. Other times, modern information overload & historical chauvinism cause us to forget ancient wisdom which stills applies. The framework for learning that I embody is inspired by three Ancient Greek maxims inscribed in the Temple of Apollo at Delphi:
- “Γνῶθι σεαυτόν” (Know thyself)
- “Μηδὲν ἄγαν” (Nothing in excess)
- “Ἐγγύα πάρα δ Ἄτα” (Certainty brings insanity)
Mind & Matter
Synapse Energetics & Fat Metabolism in the Brain | Timothy Ryan | 241
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.
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