FGF21 and obesity due to melanocortin 4 receptor deficiency: Furthermore, the beneficial effects of exercise on the alleviation of obesity-associated insulin resistance, glucose intolerance, and ectopic lipid accumulation are abrogated in adipocyte-specific Klb knockout and Fgf21 deficient mice (Geng et al, 2019; Loyd et al, 2016), supporting an obligatory role of FGF21 signaling in adipose tissue for the metabolic benefits of exercise (Fig. 2).