Depletion of adipocyte becn1 leads to lipodystrophy and metabolic dysregulation

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)182-195
Number of pages14
JournalDiabetes
Volume70
Issue number1
DOIs
Publication statusPublished - 2021 Jan

Bibliographical note

Funding Information:
Funding. This work was supported by National Research Foundation of Korea grants funded by the Korean government (Ministry of Science and ICT, NRF-2020R1A3B2078617 to J.B.K. and 2018R1A2A1A05022746, 2020R1A4A1019063, and 2019R1I1A 01058338) and in part by the Brain Korea 21 PLUS Project for Medical Science. Duality of Interest. No potential conflicts of interest relevant to this article were reported.

Publisher Copyright:
© 2020 by the American Diabetes Association.

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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