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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.*

The obesity susceptibility gene TMEM18 promotes adipogenesis through direct activation of PPARG.

Cell Rep. 33:108295 (2020)

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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, TMEM1 8 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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Adipogenesis ; Adipose Progenitor Cells ; Adipose Tissue ; Adipose Tissue Dysfunction ; Children ; Obesity ; Pparg ; Tmem18 ; Zebrafish; Genome-wide Association; Insulin-resistance; Messenger-rna; Eating Questionnaire; Dietary Restraint; Body-weight; Expression; Differentiation; Gamma; Zebrafish

ISSN (print) / ISBN 2211-1247

e-ISSN 2211-1247

Journal Cell Reports

Quellenangaben Volume: 33, Issue: 3, Article Number: 108295

Publisher Cell Press

Publishing Place 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)

Grants European Regional Development Fund
LIFE (Leipzig Research Center for Civilization Diseases, University of Leipzig) - Free State of Saxony
LIFE (Leipzig Research Center for Civilization Diseases, University of Leipzig) - European Regional Development Fund (ERDF)
LIFE (Leipzig Research Center for Civilization Diseases, University of Leipzig) - European Union
University of Leipzig
Federal Ministry of Education and Research (BMBF), Germany
Deutsche Forschungsgemeinschaft (DFG)