The mechanism(s) by which FGF21 improves hepatic steatosis are incompletely understood, but the pathway does not appear to be autocrine or paracrine because Fgfr1 is only sparsely expressed in hepatocytes (59) and because Klb-null and wildtype livers are equally responsive to FGF21 (32). Here, FGFR1 is linked to fatty liver disease.