AGRP Human

AGRP was identified due to its sequence similarity to the Agouti coat color gene product, which is a paracrine signaling molecule expressed in the skin. The Agouti gene’s transient expression during hair growth leads to the characteristic barring of coat fur in rodents . AGRP, however, is primarily expressed in the hypothalamus, particularly in neurons within the arcuate nucleus . These neurons also produce Neuropeptide Y (NP-Y), another potent orexigenic peptide .

AGRP’s primary function is to promote positive energy balance by stimulating food intake and reducing energy expenditure. It achieves this by antagonizing the melanocortin receptors, thereby inhibiting the action of alpha-melanocyte-stimulating hormone (α-MSH), which normally suppresses appetite .

The human recombinant form of AGRP is produced using Escherichia coli (E. coli) as the expression system. This recombinant protein includes a His Tag and a thrombin cleavage site, making it easier to purify and manipulate in laboratory settings . The recombinant AGRP is a 14.4 kDa protein containing 112 amino acid residues of the human AGRP and 16 additional amino acid residues from the His Tag and thrombin cleavage site .

AGRP’s biological activity is primarily attributed to its carboxyl-terminal cysteine-rich domain, which is crucial for its binding to melanocortin receptors. Studies have shown that truncated variants of AGRP, such as AGRP (87–132), retain their ability to inhibit α-MSH-induced cAMP generation at melanocortin receptors . This inhibition leads to increased food intake and body weight gain in rodents, even in the absence of hyperphagia .

AGRP levels are elevated in obese individuals compared to lean controls, and its expression increases with fasting . This suggests that AGRP plays a role in the body’s response to energy deficiency and may be a target for therapeutic interventions in obesity and metabolic disorders.