FGF21 and obesity due to melanocortin 4 receptor deficiency: Since adipocyte FGFR1 is a selective target of FGF21 and an additional target of FGF19 in addition to hepatocyte FGFR4, our results predict that this adipocyte-directed mechanism [38,39] may underpin the beneficial effects of endocrine ligands, FGF21 and FGF19, observed under conditions of not only caloric restriction, but also excess as in obesity that both cause metabolic perturbation in the liver.