Protein glycation and its markers namely AGEs and their receptor RAGE, were reported to increase in rat fed HFD, contributing NASH pathogenesis [18,19]. Based on this information and the fact that liver is the main organ to clear AGEs, it was logical to evaluate protein glycation/glycosylation in the present model. Indeed, the WT-HFD group showed markedly higher levels of AGEs, RAGE, and glycoproteins compared to the other three groups (Fig. 2). These results suggest that protein glycation/glycosylation may also play a role in the faster development of NASH in the WT-HFD mice and that the absence of CYP2E1 ameliorates/attenuates the AGEs formation. Thus, the second hit in the NASH [3] represents increased lipid peroxidation, protein oxidation, nitration, and glycation/glycosylation in the WT-HFD (Supplementary Fig. 2).
