| First Author | Hasenfuss SC | Year | 2014 |
| Journal | Cell Metab | Volume | 19 |
| Issue | 1 | Pages | 84-95 |
| PubMed ID | 24411941 | Mgi Jnum | J:210545 |
| Mgi Id | MGI:5571427 | Doi | 10.1016/j.cmet.2013.11.018 |
| Citation | Hasenfuss SC, et al. (2014) Regulation of steatohepatitis and PPARgamma signaling by distinct AP-1 dimers. Cell Metab 19(1):84-95 |
| abstractText | 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. |
