60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH

Abstract

The melanocortin peptides derived from pro-opiomelanocortin (POMC) were originally understood in terms of the biological actions of α-melanocyte-stimulating hormone (α-MSH) on pigmentation and adrenocorticotrophic hormone on adrenocortical glucocorticoid production. However, the discovery of POMC mRNA and melanocortin peptides in the CNS generated activities directed at understanding the direct biological actions of melanocortins in the brain. Ultimately, discovery of unique melanocortin receptors expressed in the CNS, the melanocortin-3 (MC3R) and melanocortin-4 (MC4R) receptors, led to the development of pharmacological tools and genetic models leading to the demonstration that the central melanocortin system plays a critical role in the regulation of energy homeostasis. Indeed, mutations in MC4R are now known to be the most common cause of early onset syndromic obesity, accounting for 2–5% of all cases. This review discusses the history of these discoveries, as well as the latest work attempting to understand the molecular and cellular basis of regulation of feeding and energy homeostasis by the predominant melanocortin peptide in the CNS, α-MSH.

Ultraviolet radiation, vitamin D and the development of obesity, metabolic syndrome and type-2 diabetes

“…65 A similar increase in plasma α-MSH levels between winter and summer has been reported in adult humans. 66 Pre-clinical studies suggest that α-MSH may prevent obesity by inhibiting feeding and enhancing catabolic signals to promote energy consumption through melanocortin-3 and -4 receptors (reviewed by 67 ). Suberythemal UVB irradiation also increases the expression of α-MSH and melanocortin-4 receptor (MC4R) in the arcuate nucleus of the hypothalamus of C57Bl/6 mice.…”

New Thoughts on Pediatric Genetic Obesity: Pathogenesis, Clinical Characteristics and Treatment Approach

“…In 1997, a role of central melanocortin signaling in the control of energy homeostasis was known [37]. Proopiomelanocortin (POMC) acts on anorectic targets of leptin in the brain [38].…”

“…The α-MSH analog RM-493 [43,44], also known as setmelanotide, was awarded orphan drug status for POMC deficiency and Prader-Willi syndrome [37].…”

Neuronal cells derived from human induced pluripotent stem cells as a functional tool of melanocortin system

“…We focused on the brain melanocortin system because of its importance in the regulation of food intake, energy expenditure and etiology of human obesity (9)(10)(11)(12)(13)(14). Among the five melanocortin receptors, melanocortin-3 receptor (MC3R) and melanocortin-4 receptor (MC4R) are distributed in the brain (15), and the activation of these receptors reduces food intake and increases energy expenditure both in rodents and human (10-15).…”