PUBLICATION

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

Authors
Landgraf, K., Klöting, N., Gericke, M., Maixner, N., Guiu-Jurado, E., Scholz, M., Witte, A.V., Beyer, F., Schwartze, J.T., Lacher, M., Villringer, A., Kovacs, P., Rudich, A., Blüher, M., Kiess, W., Körner, A.
ID
ZDB-PUB-201022-14
Date
2020
Source
Cell Reports   33: 108295 (Journal)
Registered Authors
Keywords
PPARG, TMEM18, adipogenesis, adipose progenitor cells, adipose tissue, adipose tissue dysfunction, children, obesity, zebrafish
MeSH Terms
  • 3T3-L1 Cells
  • Adipocytes/metabolism
  • Adipogenesis/genetics
  • Adipose Tissue/metabolism
  • Animals
  • Cell Differentiation/genetics
  • Cell Line
  • Female
  • Genetic Predisposition to Disease/genetics
  • Genome-Wide Association Study
  • Humans
  • Insulin Resistance/genetics
  • Male
  • Membrane Proteins/genetics*
  • Membrane Proteins/metabolism
  • Mice
  • Mice, Inbred C57BL
  • Obesity/genetics*
  • Obesity/metabolism
  • PPAR gamma/metabolism
  • Signal Transduction
  • Zebrafish
PubMed
33086065 Full text @ Cell Rep.
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping