We previously showed that ethanol-induced fatty liver using the high fat Lieber-DeCarli model was blunted in CYP2E1 KO mice as compared to WT mice [20]. These results were confirmed in the current report as evident by histopathology, oil-red staining and biochemical assay of hepatic triglyceride levels in livers from WT mice fed ethanol compared to CYP2E1 KO mice fed ethanol. We believe two important new points arise from results of Fig. 2 and 3. First, it is the absence of CYP2E1 in the KO mice and not secondary effects associated with the knockout that plays a major role in the blunting of the ethanol-induced fatty liver in the KO mice since restoring the presence of CYP2E1 in these mice restores the fatty liver. Second, human CYP2E1 was the CYP2E1 which restores the ethanol-induced steatosis, which indicates that human CYP2E1 can potentiate development of fatty liver in an oral model of chronic ethanol administration. This suggests that results on fatty liver extrapolated from rodent models of ethanol intake can be extrapolated to human models of ethanol intake with respect to effects of CYP2E1.
