PPARα expression protects male mice from high fat-induced nonalcoholic fatty liver

Mohamed A. Abdelmegeed, Seong Ho Yoo, Lauren E. Henderson, Frank J. Gonzalez, Kimberley J. Woodcroft, Byoung Joon Song

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Emerging evidence suggests that the lack of PPARα 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. Agematched 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 TNFα 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 PPARα functions may increase susceptibility to high fat-induced NASH.

Original languageEnglish
Pages (from-to)603-610
Number of pages8
JournalJournal of Nutrition
Issue number4
StatePublished - 1 Apr 2011

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Abdelmegeed, M. A., Yoo, S. H., Henderson, L. E., Gonzalez, F. J., Woodcroft, K. J., & Song, B. J. (2011). PPARα expression protects male mice from high fat-induced nonalcoholic fatty liver. Journal of Nutrition, 141(4), 603-610. https://doi.org/10.3945/jn.110.135210