De novo lipogenesis fuels adipocyte autophagosome membrane dynamics

Abstract

SummaryAutophagy is a homeostatic degradative process for cell components that enables stress resilience and can determine cellular fate and function. However, lipid sources for the rapid membrane expansions of autophagosomes, the workhorses of autophagy, are poorly understood. Here, we identify de novo lipogenesis (DNL) as a critical source of fatty acids (FA) to fuel autophagosome dynamics in adipocytes. Adipocyte fatty acid synthase (Fasn) deficiency markedly impairs autophagy, evident by autophagosome accumulation, and severely compromises degradation of the autophagic substrate p62. Autophagy dependence on FA produced by Fasn is not fully alleviated by exogenous FA in cultured adipocytes even though lipid droplet size is restored. Imaging studies reveal that Fasn colocalizes with nascent autophagosomes, while loss of Fasn decreases certain membrane phosphoinositides known to be required for autophagosome assembly. Together, our studies highlight a newly appreciated function for adipocyte DNL in autophagosome membrane formation and provide evidence that localized FA synthesis contributes to autophagosome dynamics.

SCD1 and monounsaturated lipids are required for autophagy and survival of adipocytes

“…The yeast Acyl-CoA synthetase, Fatty acid activation protein 1 (Faa1), channels fatty acids into de novo phospholipid synthesis and promotes assembly of newly synthesized phospholipids into autophagic membranes 45 . Another paper reported that FASN colocalizes with nascent autophagosomes 17 . A deficiency of FASN in adipocytes, both in vitro and in vivo, markedly impairs autophagy, causing substantial accumulation of autophagosomes 17 .…”

“…Another paper reported that FASN colocalizes with nascent autophagosomes 17 . A deficiency of FASN in adipocytes, both in vitro and in vivo, markedly impairs autophagy, causing substantial accumulation of autophagosomes 17 .…”

“…Fatty acids produced by fatty acid synthase (FASN) are essential for the autophagy process including autophagosome and lysosome maturation and fusion in adipocytes 17 . The relationships between lipogenesis and autophagy are fundamental cell biological processes in that acetyl-CoA carboxylase1 (ACC1), the rate-limiting step of fatty acid biosynthesis, promotes autophagy and survival in chronologically aging yeast 18 .…”

A review of the role of transcription factors in regulating adipogenesis and lipogenesis in beef cattle

“…It is a complicated metabolic process that is impacted by a number of variables, including nutrition, hormones and genetics. The hormone insulin, which is secreted in reaction to elevated blood glucose levels, plays a major role in controlling lipogenesis (Ladeira et al., 2016b; Rowland et al., 2023; Saponaro et al., 2015). De novo lipogenesis, a process that insulin accelerates, is a process that enhances the conversion of glucose into fatty acids in adipose tissue.…”

“…De novo lipogenesis, a process that insulin accelerates, is a process that enhances the conversion of glucose into fatty acids in adipose tissue. After that, the fatty acids are converted into triglycerides and kept in adipose tissue (Rowland et al., 2023; Yue et al., 2018). For fat deposition and metabolism in beef cattle, the interaction between adipogenesis and lipogenesis is essential.…”