Melanocortin-5 Receptor: Pharmacology and Its Regulation of Energy Metabolism

As the most recent melanocortin receptor (MCR) identified, melanocortin-5 receptor (MC5R) has unique tissue expression patterns, pharmacological properties, and physiological functions. Different from the other four MCR subtypes, MC5R is widely distributed in both the central nervous system and peripheral tissues and is associated with multiple functions. MC5R in sebaceous and preputial glands regulates lipid production and sexual behavior, respectively. MC5R expressed in immune cells is involved in immunomodulation. Among the five MCRs, MC5R is the predominant subtype expressed in skeletal muscle and white adipose tissue, tissues critical for energy metabolism. Activated MC5R triggers lipid mobilization in adipocytes and glucose uptake in skeletal muscle. Therefore, MC5R is a potential target for treating patients with obesity and diabetes mellitus. Melanocortin-2 receptor accessory proteins can modulate the cell surface expression, dimerization, and pharmacology of MC5R. This minireview summarizes the molecular and pharmacological properties of MC5R and highlights the progress made on MC5R in energy metabolism. We poInt. out knowledge gaps that need to be explored in the future.