ROS/RNS, lipid peroxidation, and protein glycation likely increase the expression of pro-inflammatory cytokines and hence increase inflammation [1,34]. Obesity and HFD are also known to induce inflammatory cytokines and increase hepatic inflammation in steatotic livers [1 and references within]. Furthermore, CYP2E1 sensitizes hepatocytes to LPS, TNFα, and oxidative injury in a p38- and JNK-dependent fashion [35]. However, the roles of various cytokines and chemokines in NAFLD are complex and sometimes inconsistent depending on the stimulating agents, exposure times (i.e., sample collection times), and evaluation of mRNA or protein levels since they might give paradoxical results [36,37]. For instance, hepatic TNFα increased first after 1 and 2 weeks of exposure to methionine-choline deficient diet and then actually decreased at 4 and 8 weeks despite the high levels of TNFα mRNA and OPN throughout the feeding periods [37]. In addition, F4/80 and high hepatic inflammatory foci have been found to be remarkably high in Mcp-1-null mice [38]. In the current model, we observed decreased intrahepatic levels of TNFα and MCP-1 in HFD-WT than the corresponding LFD-WT mice despite increased amounts of OPN
