Peroxisome proliferator-activated receptor α (PPARα) is a major regulator for hepatic lipid metabolism. PPARα regulates genes of lipid oxidation by binding to promoters of specific genes (Kersten et al., 1999; Leone et al., 1999). After ethanol feeding, PPARα was upregulated in Cyp2e1−/− mice, and consistently, Cyp2e1−/− mice developed no or little alcoholic fatty liver (Lu et al., 2008). Very interestingly, ethanol feeding did not upregulate PPARα in the Cyp2a5−/− mice although the basal level of PPARα was elevated in the Cyp2a5−/− mice; consistently, alcoholic fatty liver disease was enhanced in the Cyp2a5−/− mice (Hong et al., 2015). These results support the notion that PPARα protects against the development of alcoholic fatty liver. Indeed, Pparα knockout (Pparα−/−) mice develop more severe alcoholic fatty liver disease (Nakajima et al., 2004; Okiyama et al., 2009). PPARα generally regulates expression of lipid metabolism genes encoding acyl-CoA oxidase, carnitine palmitoyltransferase I and short chain acyl-CoA dehydrogenase (Kersten et al., 1999; Leone et al., 1999). After fasting, Pparα−/− mice develop more severe fatty liver due to impaired fat oxidation, but expression of carnitine palmitoyltransferase I and
