Impaired PPARα signalling is probably a major reason for the enhanced alcoholic liver injury in cyp2a5−/− mice, because PPARα was decreased in cyp2a5−/− mice but not in cyp2a5+/+ mice (Fig. 3C, 3D). Pparα−/− mice were used to confirm the role of PPARα in the development of alcoholic liver injury. After 3 weeks of ethanol feeding, the serum levels of ALT and AST were elevated in pparα−/− mice to a greater extent than in pparα+/+ mice (Fig 5A); serum TG was also increased in pparα−/− mice but not in pparα+/+ mice (Fig 5B). These results suggest that PPARα regulates the development of alcoholic liver injury. Liver expression of CYP2E1 and CYP2A5 was comparably induced in pparα−/− and pparα+/+ mice (Fig 5C), and also CYP2E1 and CYP2A5 activity followed a similar trend (Fig 5D), thus suggesting that the difference in alcoholic liver injury between pparα−/− and pparα+/+ mice is not due to CYP2E1 and CYP2A5.
