It was also demonstrated that FGF21 is implicated in the regulation of energy metabolism and homeostasis [16], and circulating FGF21 levels have been reported to be increased in metabolic stress conditions, such as obesity, insulin resistance, and T2D, [13, 17] and interpreted as a sort of homeostatic response to counteract the metabolic stress. Here, FGF21 is linked to obesity due to melanocortin 4 receptor deficiency.