LEP and Obesity: Variants in POMC have been linked to obesity and hyperphagia, likely through (a) leptin-dependent sympathetic innervation of adipose tissue, which then decreases the mobilization of lipids within the white adipose tissue (WAT), and (b) impaired MC4R signaling in the hypothalamus because of the lack of α-MSH and diacetyl-α-MSH, which leads to increased appetite [41–43].