ArticleNature communications2025
Non-canonical lysosomal lipolysis drives mobilization of adipose tissue energy stores with fasting.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
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Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The impact of intermittent fasting on body composition and cardiometabolic outcomes in overweight and obese adults: a systematic review and meta-analysis of randomized controlled trials.Nutrition journal · 2025Pooled it
- Lysosomes and lysosomal dysfunction in ageing biology.Nature cell biology · 2026Review
- Low lysosomal acid lipase activity is associated with histological progression of metabolic dysfunction-associated steatotic liver disease.Hepatology international · 2026Article
- Lipid metabolism dysregulation in rheumatoid arthritis: from multi-omics discovery to adjunctive therapy with conjugated linoleic acid.Arthritis research & therapy · 2026Article
- Investigating fasting for metabolic health and longevity.Biogerontology · 2026Review
- Lipolysis in Health and Disease: Pathways, Regulation, and Metabolic Consequences.Current diabetes reports · 2026Review
- Cytosolic Versus Lysosomal Lipolysis in Adipose Tissue: Opposing Roles in Cardiometabolic Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- NF-κB restrains nutrient-dependent transcription programs through chromatin modulation in Drosophila.Nucleic acids research · 2026Article
- A Critical Assessment of Fasting to Promote Metabolic Health and Longevity.Endocrine reviews · 2025Review
- Prolonged Water-Only Fasting Followed by a Whole-Plant-Food Diet Promotes Fat-Free Mass Recovery and Continued Fat Mass Loss in Adults With Overweight or Obesity.Obesity science & practice · 2025Article
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Physiological adaptations to fasting enable humans to survive for prolonged periods without food and involve molecular pathways that may drive life-prolonging effects of dietary restriction in model organisms. Mobilization of fatty acids and glycerol from adipocyte lipid stores by canonical neutral lipases, including the rate limiting adipose triglyceride lipase (Pnpla2/ATGL), is critical to the adaptive fasting response. Here we discovered an alternative mechanism of lipolysis in adipocytes involving a lysosomal program. We functionally tested lysosomal lipolysis with pharmacological and genetic approaches in mice and in murine and human adipocyte and adipose tissue explant culture, establishing dependency on lysosomal acid lipase (LIPA/LAL) and the microphthalmia/transcription factor E (MiT/TFE) family. Our study establishes a model whereby the canonical pathway is critical for rapid lipolytic responses to adrenergic stimuli operative in the acute stage of fasting, while the alternative lysosomal pathway dominates with prolonged fasting.
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Registered trials
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