Given the diverse function of POMC-derived peptides, POMC variation may affect the risk for several disease states. Peptides such as α-MSH, ACTH, and lipotrophin are involved in appetite regulation, glucose and lipid metabolism, and energy homeostasis. Polymorphisms at POMC may reasonably contribute to the development of obesity. Studies have shown an association between four POMC polymorphisms (rs1009388, rs2071345, rs1042571, and rs1866146) and obesity traits in the general population (20). In addition, α-MSH has a dual role in regulating food intake and influencing hair pigmentation, and ACTH stimulates the release of glucocorticoids and maintains adrenal activity. Rare loss-of-function mutations in POMC were found to cause severe early-onset obesity, adrenal insufficiency, and red hair pigmentation (21). The reinforcing effect of β-endorphin and its release from the hypothalamus or the pituitary to the nucleus accumbens (NAc) suggest a general involvement of β-endorphin in substance use disorders.
