Article (Scientific journals)
Regulation of steatohepatitis and PPARgamma signaling by distinct AP-1 dimers.
Hasenfuss, Sebastian C.; Bakiri, Latifa; Thomsen, Martin K. et al.
2014In Cell Metabolism, 19 (1), p. 84-95
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Keywords :
Adenoviridae/metabolism; Animals; Cell Line, Tumor; Fatty Liver/genetics/metabolism/pathology; Gene Expression Regulation; Hepatocytes/metabolism/pathology; Humans; Lipid Metabolism/genetics; Liver/metabolism/pathology; Mice; Non-alcoholic Fatty Liver Disease; PPAR gamma/genetics/metabolism; Protein Multimerization; Proto-Oncogene Proteins c-fos/genetics/metabolism; Proto-Oncogene Proteins c-jun/metabolism; Signal Transduction; Transcription Factor AP-1/metabolism
Abstract :
[en] Nonalcoholic fatty liver disease (NAFLD) affects up to 30% of the adult population in Western societies, yet the underlying molecular pathways remain poorly understood. Here, we identify the dimeric Activator Protein 1 as a regulator of NAFLD. Fos-related antigen 1 (Fra-1) and Fos-related antigen 2 (Fra-2) prevent dietary NAFLD by inhibiting prosteatotic PPARgamma signaling. Moreover, established NAFLD and the associated liver damage can be efficiently reversed by hepatocyte-specific Fra-1 expression. In contrast, c-Fos promotes PPARgamma expression, while c-Jun exerts opposing, dimer-dependent functions. Interestingly, JunD was found to be essential for PPARgamma signaling and NAFLD development. This unique antagonistic regulation of PPARgamma by distinct AP-1 dimers occurs at the transcriptional level and establishes AP-1 as a link between obesity, hepatic lipid metabolism, and NAFLD.
Disciplines :
Genetics & genetic processes
Author, co-author :
Hasenfuss, Sebastian C.
Bakiri, Latifa
Thomsen, Martin K.
WILLIAMS, Evan  ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Auwerx, Johan
Wagner, Erwin F.
External co-authors :
yes
Language :
English
Title :
Regulation of steatohepatitis and PPARgamma signaling by distinct AP-1 dimers.
Publication date :
2014
Journal title :
Cell Metabolism
ISSN :
1932-7420
Publisher :
Cell Press, United States
Volume :
19
Issue :
1
Pages :
84-95
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2014 Elsevier Inc. All rights reserved.
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