After HFD feeding, liver contents of triglyceride were increased in cyp2a5−/− mice to a greater extent than in cyp2a5+/+ mice (Fig 2 A). Consistently, HFD-induced fatty liver as indicated by lipid droplets in H&E stained liver sections was more pronounced in cyp2a5−/− mice than in cyp2a5+/+ mice (Fig 2B, 2C). Expression of adipose differentiation-related protein (ADRP), a marker of fatty liver (ref. 24), was increased in cyp2a5−/− mice more than in cyp2a5+/+ mice (Fig 2 D). Fibroblast growth factor 21 (FGF21) is mainly expressed in liver and released into blood (ref. 25). Basal levels of serum FGF21 were elevated in cyp2a5−/− mice. HFD induced FGF21 in cyp2a5+/+ mice but did not induce FGF21 in cyp2a5−/− mice (Fig 2F). As expected, there was no hepatic CYP2A expression in cyp2a5−/− mice (Fig 2 D), activity of coumarin 7-hydroxylase was almost undetectable in hepatic microsomes isolated from cyp2a5−/− mice (Fig 2 E). Even though hepatic activity coumarin 7-hydroxylase and expression of CYP2A were detectable in cyp2a5+/+ mice, they were not induced by HFD feeding (Fig 2D, 2E). CYP2E1, both activity and protein expression,
