Oxidative stress has been suggested to play a role in the advancement of NAFLD to NASH. Sources of oxidative stress include: cytochrome P450 2E1 (CYP2E1), lipid peroxidation, mitochondrial dysfunction, cytokine induction, NADPH oxidase, etc [7]. CYP2E1, a member of the oxido-reductase cytochrome family, can oxidize a variety of small molecule substrates including xenobiotics, ethanol and fatty acids [7–9]. Superoxide anion, a byproduct of the CYP2E1-mediated metabolism [7–9], is a very potent ROS, which can serve as part of the second hit to advance the severity of NAFLD. CYP2E1 expression and activity in the liver are increased in humans and in animal models of NAFLD [7,10,11] Indeed, CYP2E1 was increased in obesity, fatty liver, NASH in both human and rodents, and this increase appears to correlate well with the severity of NAFLD [7,10–12]. Thus, it would be of great interest to characterize the potential role of CYP2E1 in the advancement of NAFLD and development of NASH by using Cyp2e1-null mice as a negative control in high-fat diet (HFD)-mediated NASH models. The aim of this study was to examine this hypothesis by
