It is well known that PPARα can regulate liver fatty acid oxidation and prevent fatty liver. Fasted pparα−/− mice exhibited more severe steatosis than fasted wild type mice (ref.14–15). Global or liver-specific PPARα absence revealed an enhanced fatty liver in response to methionine and choline deficient diet (ref.32). Consistently, P-A- mice developed more severe fatty liver than P+A- mice did, and serum free fatty acids was higher in P-/A- mice and P-A+ mice than in P+/A- mice, suggesting that PPARα may synergize with CYP2A to protect against hepatic steatosis i.e. the protective effects of CYP2A on non-alcoholic fatty liver are augmented but not masked by PPARα. PPARα can also regulate glucose homeostasis (ref.33). Gluconeogenesis indicated by pyruvate tolerance test and glucose intolerance indicated by glucose tolerance test were lower in P-/A- and P-/A+ mice than in P+A- mice, suggesting that PPARα regulates gluconeogenesis and glucose homeostasis independent of CYP2A. More severe glucose and pyruvate intolerance in P+/A- mice than in P-/A- mice suggests that CYP2A regulates glucose homeostasis via PPARα. Both P-/A- mice and P-/A+ mice exhibited comparable higher serum
