Melanocortins and body weight regulation: glucocorticoids, Agouti-related protein and beyond

In the intervening three decades since Panksepp observed for the first time that centrally administered α-melanocyte stimulating hormone decreased food intake (Panksepp and Meeker, 1976), a wealth of data have accrued to firmly establish melanocortin signaling as a central regulator of food intake and fat mass. Advances in molecular biology have not only allowed detailed studies of spontaneously occurring obese mice with altered melanocortin signaling to be undertaken but also permitted the generation of a plethora of mouse models with precise perturbations at critical steps in the melanocortin system to finesse further the cellular and molecular architecture of relevant pathways. In this article we focus in upon a number of these mouse models which continue to help us tease apart the complexities of this critical system. Further, we review data on the important interaction between pro-opiomelanocortin derived peptides and the adrenal system and the relationship between agonist and antagonist peptides acting at central melanocortin receptors.