Effects of pro-opiomelanocortin (POMC) on food intake and body weight: mechanisms and therapeutic potential?

POMC (pro-opiomelanocortin) is a complex polypeptide precursor which is cleaved into smaller biologically active peptides such as the melanocortins, alpha-, beta- and gamma-melanocyte-stimulating hormone. Data from human genetic and murine studies convincingly show that an intact central melanocortin signalling pathway is critical for normal energy homoeostasis. Not only does a loss of normal melanocortin signalling lead to obesity, but there are also data implicating increased melanocortin activity in the pathogenesis of cachexia. The study of POMC biology has lead to some fundamental insights into the mechanisms controlling food intake and body weight. This increased understanding of the physiological roles of the melanocortin system has opened up the potential for the design and development of rational therapies to treat perturbations in energy homoeostasis.