What is the Origin of Melanocortin-4 Receptor (MC4R)?

The term combines "Melanocortin," referring to the class of peptide hormones that act as its ligands, and "Receptor," indicating its role as a binding site for these signaling molecules. Its designation as "4" distinguishes it from other melanocortin receptor subtypes found throughout the body. The clinical significance of MC4R emerged with the discovery of its potent, non-redundant role in regulating body weight homeostasis.

What is the Mechanism of Melanocortin-4 Receptor (MC4R)?

The MC4R is tonically inhibited by the Agouti-related peptide (AgRP) and robustly stimulated by the α-Melanocyte-stimulating hormone (α-MSH). When α-MSH binds to MC4R, it activates a downstream signaling cascade that promotes the feeling of satiety and increases total energy expenditure. Conversely, AgRP binding blocks this crucial signal, leading to increased appetite and reduced energy use. Genetic mutations that impair MC4R function disrupt this delicate energy balance, resulting in chronic positive energy balance.

Melanocortin-4 Receptor (MC4R) ∞ Area

Melanocortin-4 Receptor (MC4R)

Meaning

The Melanocortin-4 Receptor (MC4R) is a G-protein coupled receptor predominantly expressed in the hypothalamus of the brain, functioning as a critical nexus for the central regulation of energy balance, appetite, and satiety. It integrates signals from peripheral hormones like leptin and insulin, translating metabolic status into precise feeding behavior and energy expenditure commands. Dysfunction in this receptor, often due to genetic mutation, is a common genetic cause of severe early-onset obesity.