ArticleThe Journal of clinical investigation2025
Identification of lysosomal lipolysis as an essential noncanonical mediator of adipocyte fasting and cold-induced lipolysis.
Article in The Journal of clinical investigation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Secreted enzyme uptake masks the in vivo phenotype of macrophage-specific lysosomal acid lipase deletion.Molecular metabolism · 2026Article
- Lipolysis in Health and Disease: Pathways, Regulation, and Metabolic Consequences.Current diabetes reports · 2026Review
- ATP6V1B2 alleviates hepatic steatosis by promoting lysosomal acidification in hepatocytes.Cell death discovery · 2026Article
- Cytosolic Versus Lysosomal Lipolysis in Adipose Tissue: Opposing Roles in Cardiometabolic Disease.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- 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
- Assessing the efficacy of the natural disaccharide trehalose in ameliorating diet-induced obesity and metabolic dysfunction.Frontiers in nutrition · 2025Article
Corrections and comments
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Authors and funding
20 authors.
Funding
Abstract
Adipose tissue lipolysis is the process by which triglycerides in lipid stores are hydrolyzed into free fatty acids (FFAs), serving as fuel during fasting or cold-induced thermogenesis. Although cytosolic lipases are considered the predominant mechanism of liberating FFAs, lipolysis also occurs in lysosomes via lysosomal acid lipase (LIPA), albeit with unclear roles in lipid storage and whole-body metabolism. We found that adipocyte LIPA expression increased in adipose tissue of mice when lipolysis was stimulated during fasting, cold exposure, or β-adrenergic agonism. This was functionally important, as inhibition of LIPA genetically or pharmacologically resulted in lower plasma FFAs under lipolytic conditions. Furthermore, adipocyte LIPA deficiency impaired thermogenesis and oxygen consumption and rendered mice susceptible to diet-induced obesity. Importantly, lysosomal lipolysis was independent of adipose triglyceride lipase, the rate-limiting enzyme of cytosolic lipolysis. Our data suggest a significant role for LIPA and lysosomal lipolysis in adipocyte lipid metabolism beyond classical cytosolic lipolysis.
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