It has been suggested in mice that the beneficial effects of exercise—such as the alleviation of obesity-associated insulin resistance, glucose intolerance, and ectopic lipid accumulation—are abrogated in adipocyte-specific β-klotho (FGF21 receptor) knockout (158), suggesting the important role of FGF21 in mediating the metabolic benefits of exercise (154, 158). This evidence concerns the gene FGF21 and obesity due to melanocortin 4 receptor deficiency.