De novo lipogenesis fuels adipocyte autophagosome and lysosome membrane dynamics

Leslie A. Rowland (), Adilson Guilherme, Felipe Henriques, Chloe DiMarzio, Sean Munroe, Nicole Wetoska, Mark Kelly, Keith Reddig, Gregory Hendricks, Meixia Pan, Xianlin Han, Olga R. Ilkayeva, Christopher B. Newgard and Michael P. Czech ()
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Leslie A. Rowland: University of Massachusetts Chan Medical School
Adilson Guilherme: University of Massachusetts Chan Medical School
Felipe Henriques: University of Massachusetts Chan Medical School
Chloe DiMarzio: University of Massachusetts Chan Medical School
Sean Munroe: University of Massachusetts Chan Medical School
Nicole Wetoska: University of Massachusetts Chan Medical School
Mark Kelly: University of Massachusetts Chan Medical School
Keith Reddig: University of Massachusetts Chan Medical School
Gregory Hendricks: University of Massachusetts Chan Medical School
Meixia Pan: University of Texas Health Science Center at San Antonio
Xianlin Han: University of Texas Health Science Center at San Antonio
Olga R. Ilkayeva: Duke University School of Medicine
Christopher B. Newgard: Duke University School of Medicine
Michael P. Czech: University of Massachusetts Chan Medical School

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: Abstract 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.

Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37016-8

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DOI: 10.1038/s41467-023-37016-8

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