Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator (Kharitonenkov et al., 2005). FGF21 exerts its effect via binding to FGF receptor 1 (FR1) (Luo and McKeehan, 2013). FGF21 can lower blood glucose levels and enhance insulin effects on blood glucose levels (Kharitonenkov et al., 2005). FGF21 can also attenuate hepatic steatosis by regulating hepatic lipid metabolism (Badman et al., 2007). FGF21 is mainly produced in liver and liver is a major source of serum FGF21 (Luo et al., 2013). In liver, FGF21 is regulated by PPARα (Badman et al., 2007; Inagaki et al., 2007). In this study, we hypothesize that PPARα protects against alcoholic fatty liver via FGF21; and that alcoholic fatty liver is enhanced in the Cyp2a5−/− mice because the PPARα-FGF21 axis cannot be upregulated in the Cyp2a5−/− mice.
