Depletion of adipocyte becn1 leads to lipodystrophy and metabolic dysregulation

Abstract

Becn1/Beclin-1 is a core component of the class III phosphatidylinositol 3-kinase required for autophago-some formation and vesicular trafficking. Although Becn1 has been implicated in numerous diseases such as cancer, aging, and neurodegenerative disease, the role of Becn1 in white adipose tissue and related metabolic diseases remains elusive. In this study, we show that adipocyte-specific Becn1 knockout mice develop severe lipodystrophy, leading to adipose tissue inflam-mation, hepatic steatosis, and insulin resistance. Ablation of Becn1 in adipocytes stimulates programmed cell death in a cell-autonomous manner, accompanied by elevated endoplasmic reticulum (ER) stress gene expression. Fur-thermore, we observed that Becn1 depletion sensitized mature adipocytes to ER stress, leading to accelerated cell death. Taken together, these data suggest that adi-pocyte Becn1 would serve as a crucial player for adipo-cyte survival and adipose tissue homeostasis. © 2020 by the American Diabetes Association.