Hepatic steatosis increases the liver susceptibility to more serious insults like inflammation and increased oxidative/nitrosative stress, especially in the presence of oxidizable unsaturated fatty acids in steatotic livers [1,11]. The oxidation of unsaturated fatty acids can increase lipid peroxidation, which can activate hepatic stellate cells thus expediting the development of fibrosis [1,25]. Fatty acids upregulate both CYP2E1 mRNA and protein levels in cell culture models and that HFD increased CYP2E1 levels in the rat livers [7,17]. Furthermore, using ob/ob mice, obesity-mediated development of oxidative stress and liver injury were shown to be enhanced by CYP2E1 induction [30]. We also witnessed that both CYP2E1 activity and protein amounts were increased remarkably only in HFD-WT mice. This result suggests that the presence higher levels of oxidative/nitrosative stress in the WT-HFD group compared to the other groups since CYP2E1 is known to increase the generation of both ROS and RNS levels [8–10,16], leading to increased production of peroxynitrite, which can modify the function of various proteins [31]. Consistent with this view, we found that the lipid peroxidation levels and oxidized and nitrated proteins
