| First Author | Morán-Salvador E | Year | 2011 |
| Journal | FASEB J | Volume | 25 |
| Issue | 8 | Pages | 2538-50 |
| PubMed ID | 21507897 | Mgi Jnum | J:196866 |
| Mgi Id | MGI:5490027 | Doi | 10.1096/fj.10-173716 |
| Citation | Moran-Salvador E, et al. (2011) Role for PPARgamma in obesity-induced hepatic steatosis as determined by hepatocyte- and macrophage-specific conditional knockouts. FASEB J 25(8):2538-50 |
| abstractText | Peroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor central to glucose and lipid homeostasis. PPARgamma role in nonalcoholic fatty liver disease is controversial because PPARgamma overexpression is a general property of steatotic livers, but its activation by thiazolidinediones reduces hepatic steatosis. Here, we investigated hepatic PPARgamma function by using Cre-loxP technology to generate hepatocyte (PPARgamma(Deltahep))- and macrophage (PPARgamma(Deltamac))-specific PPARgamma-knockout mice. Targeted deletion of PPARgamma in hepatocytes, and to a lesser extent in macrophages, protected mice against high-fat diet-induced hepatic steatosis. Down-regulated expression of genes involved in lipogenesis (SCD1, SREBP-1c, and ACC), lipid transport (CD36/FAT, L-FABP, and MTP), and beta-oxidation (PPARalpha and ACO) was observed in PPARgamma(Deltahep) mice. Moreover, PPARgamma(Deltahep) mice showed improved glucose tolerance and reduced PEPCK expression without changes in Pcx, Fbp1, and G6Pc expression and CREB and JNK phosphorylation. In precision-cut liver slices (PCLSs) and hepatocytes, rosiglitazone either alone or in combination with oleic acid increased triglyceride accumulation, an effect that was blocked by the PPARgamma antagonist biphenol A diglycidyl ether (BADGE). PCLSs and hepatocytes from PPARgamma(Deltahep) mice showed blunted responses to rosiglitazone and oleic acid, whereas the response to these compounds remained intact in PCLSs from PPARgamma(Deltamac) mice. Collectively, these findings establish PPARgamma expression in hepatocytes as a prosteatotic factor in fatty liver disease. |
