The Obesity-Susceptibility Gene TMEM18 Promotes Adipogenesis through Activation of PPARG

Kathrin Landgraf, Nora Klöting, Martin Gericke, Nitzan Maixner, Esther Guiu-Jurado, Markus Scholz, A. Veronica Witte, Frauke Beyer, Julian T. Schwartze, Martin Lacher, Arno Villringer, Peter Kovacs, Assaf Rudich, Matthias Blüher, Wieland Kiess, Antje Körner

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

TMEM18 is the strongest candidate for childhood obesity identified from GWASs, yet as for most GWAS-derived obesity-susceptibility genes, the functional mechanism remains elusive. We here investigate the relevance of TMEM18 for adipose tissue development and obesity. We demonstrate that adipocyte TMEM18 expression is downregulated in children with obesity. Functionally, downregulation of TMEM18 impairs adipocyte formation in zebrafish and in human preadipocytes, indicating that TMEM18 is important for adipocyte differentiation in vivo and in vitro. On the molecular level, TMEM18 activates PPARG, particularly upregulating PPARG1 promoter activity, and this activation is repressed by inflammatory stimuli. The relationship between TMEM18 and PPARG1 is also evident in adipocytes of children and is clinically associated with obesity and adipocyte hypertrophy, inflammation, and insulin resistance. Our findings indicate a role of TMEM18 as an upstream regulator of PPARG signaling driving healthy adipogenesis, which is dysregulated with adipose tissue dysfunction and obesity.

Original languageEnglish
Article number108295
JournalCell Reports
Volume33
Issue number3
DOIs
StatePublished - 20 Oct 2020

Keywords

  • PPARG
  • TMEM18
  • adipogenesis
  • adipose progenitor cells
  • adipose tissue
  • adipose tissue dysfunction
  • children
  • obesity
  • zebrafish

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