FGF21 is a novel metabolic regulator modulating glucose and lipid metabolism (Kharitonenkov et al., 2005). Ethanol feeding caused a 3-fold increase in serum FGF21 in Cyp2a5+/+ mice, however, ethanol feeding had no effect on serum FGF21 in Cyp2a5−/− mice probably because basal levels of serum FGF21 in Cyp2a5−/− mice were already elevated (Fig 2A). Consistently, liver FGF21 expression was also induced by ethanol feeding in Cyp2a5+/+ mice. In Cyp2a5−/− mice, however, ethanol feeding did not induce hepatic FGF21 expression although basal FGF21 expression in liver was already higher compared to Cyp2a5+/+ mice (Fig 2B). Liver FGF21 is regulated by PPARα (Badman et al., 2007; Inagaki et al., 2007). Basal PPARα expression in Cyp2a5−/− mice was higher than that in Cyp2a5+/+ mice although ethanol reduced PPARα expression in both the Cyp2a5−/− mice and Cyp2a5+/+ mice (Fig 2B, C).
