Melanocortins are derived from posttranslational processing of the precursor
protein pro-opiomelanocortin (
POMC). The central melanocortinergic system consists of endogenous agonist
alpha-melanocyte-stimulating hormone, the naturally occurring antagonist
Agouti-related protein (AGRP), and two
melanocortin receptors (MC3R, MC4R). Activation of central
melanocortin receptors inhibits feeding and leads to
weight loss, whereas blockade of the central
melanocortin signaling pathway increases food consumption and promotes
weight gain. This review will focus on the role of central
melanocortin signaling in eating behavior and will evaluate studies of the neural pathways of
POMC and AGRP systems, the effects of the central melanocortinergic system on food intake and
body weight, and the regulation of hypothalamic
POMC and AGRP neurons in response to altered feeding state and energy balance. In addition, this review will explore what is known about the interplay between the central melanocortinergic system and peripheral signals of energy homeostasis, i.e.,
leptin and
glucocorticoids. Furthermore, evidence will be presented that genetic defects within the
melanocortin signaling system are involved in determining susceptibility to
obesity and
anorexia in humans, and the therapeutic potential of
melanocortin agonists and antagonists in the treatment of these disorders will be discussed.