Hepatic CYP2A5/2A6 is reported up-regulated in various pathophysiological liver damages and induced by structurally variable hepatotoxic chemicals (Jounaidi et al., 1994; Pelkonen et al., 1997; Sipowicz et al., 1997; Raunio et al., 1998; Montero et al., 1999), including NAFLD (Wang C. et al., 2016). In all of these conditions, lipid accumulation in hepatocytes always occurs at the early stage of liver damage and results in redox status disorder in hepatocytes, which contributes to the second hit. Nrf2 is a transcription factor that activated by oxidative stress and regulates the transcription of numerous cytoprotective target genes. Our former researches showed that hepatic Nrf2 and CYP2A5 mRNA expressions were increased significantly in HFD fed mice (Wang C. et al., 2016) and accompanied with badly hepatic 18-carbon FA (SA, OA, LA, and ALA) accumulation, which is the most abundant component of liver FA (Wang X. et al., 2016). Meanwhile, mice primary hepatocytes treated with 18-carbon FA also express more Nrf2 and CYP2A5 than the control cells (Cui et al., 2016). Thus, we hypothesize that HFD-induced hepatic 18-carbon FA accumulation up-regulates CYP2A5 in hepatocytes
