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  The obesity-susceptibility gene TMEM18 promotes adipogenesis through activation of PPARG

Landgraf, K., Klöting, N., Gericke, M., Maixner, N., Guiu-Jurado, E., Scholz, M., et al. (2020). The obesity-susceptibility gene TMEM18 promotes adipogenesis through activation of PPARG. Cell Reports, 33(3): 108295. doi:10.1016/j.celrep.2020.108295.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0007-4C8D-6 Version Permalink: http://hdl.handle.net/21.11116/0000-0007-4C8E-5
Genre: Journal Article

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 Creators:
Landgraf, Kathrin1, Author
Klöting, Nora2, Author
Gericke, Martin3, Author
Maixner, Nitzan4, Author
Guiu-Jurado, Esther5, Author
Scholz, Markus6, Author
Witte, A. Veronica7, Author              
Beyer, Frauke7, Author              
Schwartze, Julian T.1, Author
Lacher, Martin8, Author
Villringer, Arno7, Author              
Kovacs, Peter5, Author
Rudich, Assaf4, Author
Blüher, Matthias2, Author
Kiess, Wieland1, Author
Körner, Antje1, Author
Affiliations:
1Center for Pediatric Research Leipzig (CPL), University Hospital Leipzig, Germany, ou_persistent22              
2Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG), Leipzig, Germany, ou_persistent22              
3Institute of Anatomy, University of Leipzig, Germany, ou_persistent22              
4Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer Sheva, Israel, ou_persistent22              
5Department of Endocrinology, Nephrology, Rheumatology, University of Leipzig, Germany, ou_persistent22              
6Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Germany, ou_persistent22              
7Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              
8Department of Pediatric Surgery, University Hospital Leipzig, Germany, ou_persistent22              

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Free keywords: TMEM18; Adipose progenitor cells; Adipogenesis; PPARG; Adipose tissue; Children; Obesity; Zebrafish; Adipose tissue dysfunction
 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.

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Language(s): eng - English
 Dates: 2020-08-252019-10-182020-09-302020-10-20
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.celrep.2020.108295
PMID: 33086065
 Degree: -

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Project name : -
Grant ID : SFB 1052/2
Funding program : -
Funding organization : Deutsche Forschungsgemeinschaft (DFG)
Project name : -
Grant ID : FKZ 01EO1501
Funding program : -
Funding organization : Federal Ministry of Education and Research (BMBF)

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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 33 (3) Sequence Number: 108295 Start / End Page: - Identifier: ISSN: 2211-1247
CoNE: https://pure.mpg.de/cone/journals/resource/2211-1247