Agouti-Related Protein (AgRP)

Clinical Significance:
Agouti-related peptide (AgRP) is a potent orexigenic (appetite-stimulating) neuropeptide with high homology to Agouti, a protein that regulates coat color in mice by inhibiting alpha Melanocyte Stimulating Hormone (αMSH). Human AgRP is 132-amino acids and is implicated in energy regulation and homeostasis. AgRP modulates it activity by acting as an antagonist to the binding of αMSH to melanocortin receptors 3 and 4 (1). It is expressed mainly in the adrenal gland and in a subset of the hypothalamus. Hypothalamic AgRP was shown to be elevated in obese and diabetic men and its overexpression led to obesity (2).  AgRP has also been shown to regulate hypothalamic-pituitary axis by affecting the expression of ACTH, prolactin, and TRH (1).

Additionally, Ghrelin, secreted by the gut, has been shown to act on stimulating feeding and body weight fain through the activation of neuropeptide Y (NPY) and AgRP (3). Since it plays a role in human energy homeostasis, gene mutations or altered levels of AgRP expression were associated with obesity and appetite regulation in diseases such as anorexia, high body mass index and type II diabetes (4). AgRP is elevated by fasting and other physiological states where food intake is necessary. Its levels are suppressed in response to satiety (5).

Reference Range:
27 – 116 pg/mL

Procedure:
AgRP is measured by direct ELISA.

Patient Preparation:
No special patient preparation is necessary.

Specimen Collection:
Collect using 10mL blood directly into ISI’s Z-tubeTM preservative, and separate as soon as possible. Freeze plasma immediately after separation. Special Z-tubeTM preservatives are available from ISI. Minimum specimen size is 1 ml.

Shipping Instructions:
Ship specimens strictly frozen in dry ice.

References:

  1. Ilnytska, O, and G Argyropoulos. “The role of the Agouti-Related Protein in energy balance regulation.” Cellular and molecular life sciences : CMLS vol. 65,17 (2008): 2721-31. doi:10.1007/s00018-008-8104-4.
  2. Shutter JR, Graham M, Kinsey AC, Scully S, Luthy R, Stark KL. Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev. 1997;11:593–602
  3. Kamegai J, Tamura H, Shimizu T, Ishii S, Sugihara H, Wakabayashi I. Chronic central infusion of ghrelin increases hypothalamic neuropeptide Y and Agouti-related protein mRNA levels and body weight in rats. Diabetes. 2001;50:2438–43.
  4. Argyropoulos, G et al. “The agouti-related protein and body fatness in humans.” International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity vol. 27,2 (2003): 276-80. doi:10.1038/sj.ijo.802201
  5. Hillebrand JJ, Kas MJ, Scheurink AJ, van Dijk G, Adan RA. AgRP(83-132) and SHU9119 differently affect activity-based anorexia. Eur. Neuropsychopharmacol. 2006;16:403–12.