What is the Origin of Agouti-Related Peptide (AgRP)?

The nomenclature is derived from the Agouti gene, which originally described a coat color pattern in mice; the related peptide in the central nervous system was subsequently identified for its profound role in regulating feeding behavior. AgRP originates exclusively from a specific population of neurons within the hypothalamic arcuate nucleus that co-express Neuropeptide Y (NPY). This hypothalamic circuit represents an evolutionarily conserved pathway for the fundamental control of energy balance.

What is the Mechanism of Agouti-Related Peptide (AgRP)?

AgRP functions as a long-lasting, competitive antagonist at the melanocortin 3 and 4 receptors (MC3R and MC4R) located on secondary neurons in the paraventricular nucleus. By blocking the binding of the anorexigenic hormone α-Melanocyte-Stimulating Hormone (α-MSH), AgRP effectively inhibits the satiety signal. This antagonistic action strongly promotes positive energy balance by driving increased food intake and simultaneously reducing energy dissipation.

Agouti-Related Peptide (AgRP)

Meaning

Agouti-Related Peptide (AgRP) is a potent orexigenic neuropeptide produced primarily in the arcuate nucleus of the hypothalamus, serving as a powerful appetite stimulant. This endogenous peptide is a critical component of the body’s complex energy homeostasis system, acting to promote food-seeking behavior and decrease overall energy expenditure. Its expression is inversely regulated by circulating metabolic signals, such as leptin and insulin, which reflect the body’s nutritional status. The peptide’s sustained action is key to survival during periods of caloric deficit.