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TMBIM1 is an inhibitor of adipogenesis and its depletion promotes adipocyte hyperplasia and improves obesity-related metabolic disease.

Abstract
Obesity is characterized by the excessive accumulation of the white adipose tissue (WAT), but healthy expansion of WAT via adipocyte hyperplasia can offset the negative metabolic effects of obesity. Thus, identification of novel adipogenesis regulators that promote hyperplasia may lead to effective therapies for obesity-induced metabolic disorders. Using transcriptomic approaches, we identified transmembrane BAX inhibitor motif-containing 1 (TMBIM1) as an inhibitor of adipogenesis. Gain or loss of function of TMBIM1 in preadipocytes inhibited or promoted adipogenesis, respectively. In vivo, in response to caloric excess, adipocyte precursor (AP)-specific Tmbim1 knockout (KO) mice displayed WAT hyperplasia and improved systemic metabolic health, while overexpression of Tmbim1 in transgenic mice showed the opposite effects. Moreover, mature adipocyte-specific Tmbim1 KO did not affect WAT cellularity or nutrient homeostasis. Mechanistically, TMBIM1 binds to and promotes the autoubiquitination and degradation of NEDD4, which is an E3 ligase that stabilizes PPARĪ³. Our data show that TMBIM1 is a potent repressor of adipogenesis and a potential therapeutic target for obesity-related metabolic disease.
AuthorsGuang-Nian Zhao, Zheng-Wei Tian, Tian Tian, Zhi-Peng Zhu, Wen-Jie Zhao, Han Tian, Xu Cheng, Feng-Jiao Hu, Man-Li Hu, Song Tian, Ting Ding, Siping Chen, Yan-Xiao Ji, Peng Zhang, Xiao-Jing Zhang, Zhi-Gang She, Yufeng Yuan, Wenping Chen, Lan Bai, Hongliang Li
JournalCell metabolism (Cell Metab) Vol. 33 Issue 8 Pg. 1640-1654.e8 (08 03 2021) ISSN: 1932-7420 [Electronic] United States
PMID34107313 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2021 Elsevier Inc. All rights reserved.
Chemical References
  • Grina protein, mouse
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RECS1 protein, mouse
Topics
  • Adipocytes, White (metabolism)
  • Adipogenesis
  • Adipose Tissue, White (metabolism)
  • Animals
  • Hyperplasia (metabolism)
  • Membrane Proteins
  • Metabolic Diseases (metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins
  • Obesity (metabolism)

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