Hasenfuss, Sebastian C.Bakiri, LatifaThomsen, Martin K.Williams, Evan G.Auwerx, JohanWagner, Erwin F.2014-01-142014-01-142014-01-14201410.1016/j.cmet.2013.11.018https://infoscience.epfl.ch/handle/20.500.14299/99505WOS:000329431200011Nonalcoholic 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.Ppar gammaSteatohepatitisNASHtext::journal::journal article::research article