Phytol enhances catalase-dependent ethanol metabolism in liver independent of PPARα.

There is an interaction between peroxisomal fatty acid β-oxidation and catalase-dependent ethanol metabolism. H2O2 is essential for catalase to metabolize ethanol. Peroxisomal fatty acid β-oxidation rate limiting enzyme is acyl-CoA oxidase (ACOX), which generates H2O2 for catalase to metabolize ethanol. Usually, ACOX1 oxidizes very long-chain fatty acids and ACOX2 oxidizes branched-chain fatty acids. Previously we reported that PPARα agonist WY-14,643 induced ACOX1 to ameliorate alcoholic steatosis, and the induced ACOX1 coordinated with the induced catalase to enhance ethanol metabolism. In this study, we examined the effects of phytol on alcoholic steatosis and ethanol metabolism. Phytol is a precursor of pristanic acid, a substrate for ACOX2. Phytol can also induce ACOX1 and catalase. Phytol was added in the Lieber-DeCarli liquid diets up to 0.2 %. After 3 weeks of feeding, phytol induced ACOX1 to ameliorate alcoholic steatosis, which was not observed in the Pparα-/- mice, implicating that the induction of ACOX1 is essential for protection against alcoholic steatosis. Phytol also enhanced ethanol metabolism, and among the ethanol metabolizing enzymes, only catalase was induced by phytol, suggesting that phytol enhances catalase-dependent ethanol metabolism. However, unlike WY-14,643, phytol induced catalase to enhance ethanol metabolism in a PPARα-independent manner because phytol but not WY-14,643 still induced catalase to enhance ethanol metabolism in the Pparα-/- mice, suggesting that ACOX1 is dispensable for catalase-dependent ethanol metabolism. It is possible that when phytol cannot induce ACOX1 in the Pparα-/- mice, phytol-derived pristanic acid is still oxidized by ACOX2 to generate H2O2 for catalase metabolism of ethanol.