According to former reports of our lab, Nrf2 and CYP2A5 mRNA expressions were both elevated in mouse model of hepatocytes steatosis (Wang C. et al., 2016) accompanied with 18-carbon FA accumulation in the hepatocytes (Wang X. et al., 2016). In mouse primary hepatocytes treated with 18-carbon FA, Nrf2, and CYP2A5 expressions were increased (Cui et al., 2016). We hypothesize that the common stimulus for up-regulation of CYP2A5/2A6 in liver damages caused by various structurally unrelated chemicals is hepatocellular FA accumulation (generally the early stage of liver damages), and Nrf2 is a potential mechanism by which 18-carbon FA induces CYP2A5/2A6 expression. Our objective is to investigate the relationship between hepatocellular 18-carbon FA accumulation and CYP2A5/2A6 expression and the involvement of Nrf2 in the process by (i) investigating the effects of hepatic steatosis on CYP2A5 expression via Nrf2 in Nrf2-null and wild type (WT) mice fed with HFD, (ii) examining the effects of 18-carbon FA [stearic acid (SA, C18:0), oleic acid (OA, C18:1), linoleic acid (LA, C18:2), and alpha-linolenic acid (ALA, C18:3)], which significantly accumulated in the HFD fed mice liver, on
