De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics.

Autor: Rowland LA; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. Leslie.rowland@umassmed.edu., Guilherme A; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA., Henriques F; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA., DiMarzio C; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA., Munroe S; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA., Wetoska N; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA., Kelly M; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA., Reddig K; Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA., Hendricks G; Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA., Pan M; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA., Han X; Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA.; Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229, USA., Ilkayeva OR; Duke Molecular Physiology Institute, Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University School of Medicine, Durham, NC, 27710, USA., Newgard CB; Duke Molecular Physiology Institute, Department of Medicine, Division of Endocrinology, Metabolism and Nutrition, Duke University School of Medicine, Durham, NC, 27710, USA., Czech MP; Program in Molecular Medicine, University of Massachusetts Chan Medical School, Worcester, MA, 01605, USA. Michael.Czech@umassmed.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2023 Mar 13; Vol. 14 (1), pp. 1362. Date of Electronic Publication: 2023 Mar 13.
DOI: 10.1038/s41467-023-37016-8
Abstrakt: Adipocytes robustly synthesize fatty acids (FA) from carbohydrate through the de novo lipogenesis (DNL) pathway, yet surprisingly DNL contributes little to their abundant triglyceride stored in lipid droplets. This conundrum raises the hypothesis that adipocyte DNL instead enables membrane expansions to occur in processes like autophagy, which requires an abundant supply of phospholipids. We report here that adipocyte Fasn deficiency in vitro and in vivo markedly impairs autophagy, evident by autophagosome accumulation and severely compromised degradation of the autophagic substrate p62. Our data indicate the impairment occurs at the level of autophagosome-lysosome fusion, and indeed, loss of Fasn decreases certain membrane phosphoinositides necessary for autophagosome and lysosome maturation and fusion. Autophagy dependence on FA produced by Fasn is not fully alleviated by exogenous FA in cultured adipocytes, and interestingly, imaging studies reveal that Fasn colocalizes with nascent autophagosomes. Together, our studies identify DNL as a critical source of FAs to fuel autophagosome and lysosome maturation and fusion in adipocytes.
(© 2023. The Author(s).)
Databáze: MEDLINE
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