Fat accumulation in the liver may be associated with decreased lipid oxidation and increased lipogenesis. The levels of fatty acid synthase (FAS), a major lipogenic enzyme, were higher in control diet-fed cyp2a5−/− mice than cyp2a5+/+ mice, but the enzyme was down-regulated by ethanol feeding to the same extent (around 50%) in cyp2a5−/− and cyp2a5+/+ mice (Fig 3C and D), thus suggesting that FAS inhibition does not contribute to the more pronounced fatty liver in cyp2a5−/− mice. AMP-activated protein kinase (AMPK) is also a regulator of lipid metabolism. Inhibition of AMPK plays a key role in ethanol-induced fatty liver by enhancing lipogenesis and depressing the rate of fatty acid β-oxidation (20). However, after ethanol feeding, we did not observe any difference in the ratio of p-AMPK/T-AMPK between cyp2a5+/+ and cyp2a5−/− mice (Fig 3C and D). PPARα regulates mitochondrial and peroxisomal fatty 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
