in cyp2a5−/− than cyp2a5+/+ mice, suggesting that there is a more active lipid metabolism in cyp2a5−/− mice than cyp2a5+/+ mice. After ethanol feeding, FAS was comparably decreased in cyp2a5−/− and cyp2a5+/+ mice, while AOX was decreased in cyp2a5−/− mice but not in cyp2a5+/+ mice. AOX is regulated by PPARα, and basal levels of PPARα are also higher in cyp2a5−/− than cyp2a5+/+ mice. It was reported that pparα−/− mice developed more pronounced alcoholic fatty liver (31). Indeed, we also found that after 3 weeks of ethanol feeding serum ALT, AST, and TG were significantly increased in Pparα−/− mice but not in pparα+/+ mice (Figure 5A, 5B), suggesting that PPARα protects against alcoholic liver injury. However, CYP2E1 and CYP2A5 levels were comparable in pparα−/− and pparα+/+ mice (Figure 5C, 5D), suggesting that PPARα regulates lipid oxidation independently of CYP2E1 and CYP2A5.
