PPARα plays an important role in the development of alcoholic fatty liver disease (Nakajima et al., 2004; Okiyama et al., 2009). Although a comparable increase in liver TG was observed in Pparα−/− mice and Pparα+/+ mice (Fig 4B), ethanol-induced hypertriglyceridemia was observed in Pparα−/− mice rather than in Pparα+/+ mice (Fig 4C). Administration of rFGF21 blunted the increase in liver TG in Pparα+/+ mice (Fig 4B) and the increase in serum TG in Pparα−/− mice (Fig 4C). PPARα and rFGF21 had no effects on liver CYP2E1 and CYP2A5 activities (Fig 4D). These results suggest that the enhanced alcoholic fatty liver found in Pparα−/− mice is associated with the lower FGF21 levels.
