Oct 29 • 💪 Physical & Mental
New research paper on fasting, autophagy and advanced fat loss
Read it here:
My review is as follows ->
Core finding:
- The paper shows a second fat-mobilizing system in adipocytes.
- Early fasting and adrenergic stress rely on the canonical neutral lipases, with ATGL as the rate-limiting enzyme.
- Prolonged fasting shifts control to a lysosomal pathway that uses lysosomal acid lipase (LAL/LIPA) and is driven by MiT/TFE transcription factors (TFEB, TFE3, MITF).
- Blocking lysosomes pharmacologically or genetically reduces fasting-induced release of free fatty acids and glycerol in mice.
- Human support: nutrient restriction in human adipocytes and human fat explants also shows LIPA-dependent lipolysis.
Simple physiology model (sequence during a fast):
- 0–6 h: post-absorptive. Glycogen supplies glucose. Lipolysis is low.
- 6–12 h: rising catecholamines. ATGL-dependent lipolysis increases. Free fatty acids rise.
- ~12–24+ h: shift in adipocytes. Lysosomal program ramps up (TFEB/TFE3/MITF↑, LAL↑). LIPA-dependent lipolysis dominates. Ketones rise. Glucose falls.
- Refeed: lysosomal signals ease; other lipases and lipogenesis genes change again.
Bottom line:
- Fasting uses two lipolytic systems with different time courses.
- ATGL handles rapid responses.
- Lysosomal LIPA handles prolonged fat mobilization.
- For advanced fat loss, design fasting that regularly enters the ≥12–24 h window, manage refeeds, and support with electrolytes and sensible activity.
- This approach aligns physiology with practice and may improve consistency in fat loss beyond short fasts.
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New research paper on fasting, autophagy and advanced fat loss
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