Depletion of adipocyte Becn1 leads to lipodystrophy and metabolic dysregulation

Abstract

<i>Becn1</i>/Beclin-1<i> </i>is a core component of the class III phosphatidylinositol 3-kinase required for autophagosome formation and vesicular trafficking. Although <i>Becn1</i> has been implicated in numerous diseases such as cancer, aging, and neurodegenerative disease, the role of <i>Becn1</i> in white adipose tissue and related metabolic diseases remains elusive. Here we show that adipocyte-specific <i>Becn1</i> knockout mice develop severe lipodystrophy, leading to adipose tissue inflammation, hepatic steatosis, insulin resistance. Ablation of <i>Becn1</i> in adipocytes stimulates programmed cell death in a cell-autonomous manner, accompanied by elevated ER stress gene expression. Furthermore, we observed that <i>Becn1 </i>depletion sensitized mature adipocytes to ER stress, leading to accelerated cell death. Taken together, these data suggest that adipocyte <i>Becn1</i> would serve as a crucial player for adipocyte survival and adipose tissue homeostasis.