It appears that ethanol-induced steatosis may be related to oxidative stress as shown by Diluzio [48] who reported that antioxidants can prevent the ethanol-induced fatty liver, and studies showing that overexpression of the copper-zinc superoxide dismutase-1 can partially reduce the ethanol steatosis [49]. CYP2E1-generated ROS contributes to the ethanol-induced oxidant stress which may explain its role in the ethanol-induced steatosis. However, mechanisms for ethanol-induced steatosis are likely to be more complex than increases in CYP2E1/cytokines/oxidant stress e.g ethanol did not induce fatty liver in C1q knockout mice despite elevating CYP2E1, TNFα, IL-6 and oxidant stress and the authors suggested a role for the classical complement pathway in contributing to the pathogenesis of ethanol-induced liver injury [50]. Blockade of PPARα function by chronic ethanol administration plays a key role in the mechanism of ethanol-induced steatosis [51] as PPARα knockout mice fed ethanol develop extensive fatty liver and liver injury [52] whereas PPARα activating ligands such as clofibrate [53] or WY14643 [51] decrease the ethanol fatty liver. Levels of PPARα, and a downstream target of PPARα, AOX, were decreased more than 50%
