CYP2E1 produces high levels of ROS [7–9] and plays a role in the formation of peroxynitrite [16,24]. The pathological role of CYP2E1 in the development of both alcoholic steatohepatitis [25] and NASH [26,27] has been suggested and thus our main aim was to evaluate the hypothesis that HFD-exposed Cyp2e1-null mice are less susceptible to NASH compared with WT-HFD. Only the WT-HFD group achieved a NAS of 5, which is qualified as NASH [14], because of higher levels of TG and lobular inflammation in WT-HFD than the null-HFD. No significant differences in the ratios of liver to body weights and plasma transaminase levels were observed among all four groups. It was previously reported that an underlying hepatic disorder can exist without the concomitant elevation of liver transaminases [10,11,28]. Thus, the presence of CYP2E1 is important in NASH development in WT-HFD. This result is consistent with a previous study that Cyp2e1-null mice are less vulnerable to alcoholic fatty liver [29].
