| First Author | Abdelmegeed MA | Year | 2011 |
| Journal | J Nutr | Volume | 141 |
| Issue | 4 | Pages | 603-10 |
| PubMed ID | 21346097 | Mgi Jnum | J:170838 |
| Mgi Id | MGI:4947467 | Doi | 10.3945/jn.110.135210 |
| Citation | Abdelmegeed MA, et al. (2011) PPAR{alpha} Expression Protects Male Mice from High Fat-Induced Nonalcoholic Fatty Liver. J Nutr 141(4):603-10 |
| abstractText | Emerging evidence suggests that the lack of PPARalpha enhances hepatic steatosis and inflammation in Ppara-null mice when fed a high-fat diet (HFD). Thus, the aim of this study was to determine whether Ppara-null mice are more susceptible to nonalcoholic steatohepatitis (NASH) than their wild-type (WT) counterparts following short-term feeding with a HFD. Age-matched male WT and Ppara-null mice were randomly assigned to consume ad libitum a standard Lieber-DeCarli liquid diet (STD) (35% energy from fat) or a HFD (71% energy from fat) for 3 wk. Liver histology, plasma transaminase levels, and indicators of oxidative/nitrosative stress and inflammatory cytokines were evaluated in all groups. Levels of lobular inflammation and the NASH activity score were greater in HFD-exposed Ppara-null mice than in the other 3 groups. Biochemical analysis revealed elevated levels of ethanol-inducible cytochrome P450 2E1 and TNFalpha accompanied by increased levels of malondialdehyde as well as oxidized and nitrated proteins in Ppara-null mice. Elevated oxidative stress and inflammation were associated with activation of c-Jun-N-terminal kinase and p38 kinase, resulting in increased hepatocyte apoptosis in Ppara-null mice fed a HFD. These results, with increased steatosis, oxidative stress, and inflammation observed in Ppara-null mice fed a HFD, demonstrate that inhibition of PPARalpha functions may increase susceptibility to high fat-induced NASH. |
