Regulation of Steatohepatitis and PPARγ Signaling by Distinct AP-1 Dimers

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 PPARγ signaling. Moreover, established NAFLD and the associated liver damage can be efficiently reversed by hepatocyte-specific Fra-1 expression. In contrast, c-Fos promotes PPARγ expression, while c-Jun exerts opposing, dimer-dependent functions. Interestingly, JunD was found to be essential for PPARγ signaling and NAFLD development. This unique antagonistic regulation of PPARγ by distinct AP-1 dimers occurs at the transcriptional level and establishes AP-1 as a link between obesity, hepatic lipid metabolism, and NAFLD.


Published in:
Cell Metabolism, 19, 1, 84-95
Year:
2014
Publisher:
Cambridge, Elsevier
ISSN:
1550-4131
Keywords:
Laboratories:




 Record created 2014-01-14, last modified 2018-03-17


Rate this document:

Rate this document:
1
2
3
 
(Not yet reviewed)