Depletion of adipocyte Becn1 leads to lipodystrophy and metabolic dysregulation
figureposted on 11.12.2020, 17:23 by Ada Admin, Young Jin, Yul Ji, Yaechan Song, Sung Sik Choe, Yong Geun Jeon, Heeju Na, Tae Wook Nam, Hye Jeong Kim, Hahn Nahmgoong, Sung Min Kim, Jae-woo Kim, Ki Taek Nam, Je Kyung Seong, Daehee Hwang, Chan Bae Park, In Hye Lee, Jae Bum Kim, Han-Woong Lee
Becn1/Beclin-1 is a core component of the class III phosphatidylinositol 3-kinase required for autophagosome 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. Here we show that adipocyte-specific Becn1 knockout mice develop severe lipodystrophy, leading to adipose tissue inflammation, hepatic steatosis, insulin resistance. Ablation of Becn1 in adipocytes stimulates programmed cell death in a cell-autonomous manner, accompanied by elevated ER stress gene expression. Furthermore, we observed that Becn1 depletion sensitized mature adipocytes to ER stress, leading to accelerated cell death. Taken together, these data suggest that adipocyte Becn1 would serve as a crucial player for adipocyte survival and adipose tissue homeostasis.