Understanding melanocortin-4 receptor control of neuronal circuits: Toward novel therapeutics for obesity syndrome

Abstract

It is well known that melanocortin-4 receptors (MC4Rs) and central melanocortin pathways regulate food intake, energy expenditure, and glucose homeostasis. Importantly, MC4R deficiency is the most common monogenic cause of human obesity. Interestingly, MC4Rs expressed by distinct central nuclei are responsible for the different physiological function of MC4R stimulation. In addition, MC4Rs activate multiple intracellular and/or synaptic signaling molecules for the regulation of neuronal circuits. Therefore, MC4Rs and the downstream signal molecules are plausible targets for development of novel therapeutics against obesity and obesity-related metabolic disorders. In this review, we discuss recent findings on the neuronal circuits and signaling molecules that are responsible for MC4R control energy balance and autonomic function. Further, we review status of MC4R agonists as novel therapeutics for obesity syndrome. We believe that comprehensive understanding of signaling molecules involved in MC4R control of neuronal circuits will help to design MC4R agonists as safe and effective anti-obesity drugs.