acid oxidation. AOX, a target gene of PPARα, is a key enzyme in peroxisomal fatty oxidation, and CPT I, another PPARα-regulated enzyme, is involved in mitochondrial fatty acid oxidation (21, 22). We previously reported that after ethanol feeding PPARα and AOX were upregulated in cyp2e1−/− mice but not in WT mice, which might be a reason why no or little alcoholic fatty liver was observed in cyp2e1−/− mice (17). Like FAS, the basal levels of PPARα and AOX were higher in cyp2a5−/− mice than cyp2a5+/+ mice; however, after ethanol feeding, PPARα and AOX were up-regulated in cyp2a5+/+ mice, but were down-regulated in cyp2a5−/− mice (Fig 3C and D). Additionally, we found no change in CPT I expression after ethanol feeding (Fig 3C and D). These results suggest that the inhibited PPARα may contribute to the more pronounced alcoholic fatty liver in cyp2a5−/− mice via regulating AOX (the peroxisomal fatty acid oxidation) but not CPT I (the mitochondrial fatty acid oxidation).
