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Gene Review

Agrp  -  agouti related neuropeptide

Rattus norvegicus

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Disease relevance of Agrp

  • In contrast, Agrp mRNA concentrations remained suppressed by 45% in the pair-fed group after 7 days of AGRP infusion despite equal body weight compared to saline controls [1].
  • The obesity observed following CNS administration of Agrp is the result of decreased energy expenditure and increased food intake [2].

High impact information on Agrp

  • Intracerebroventricular (ICV) administration of Agrp (83-132) decreased plasma thyroid stimulating hormone (TSH) in fed male rats [3].
  • This study indicates that the hypothalamic nuclei expressing MC4R vary in their sensitivity to Agrp and alpha-MSH with regard to their effect on feeding [4].
  • No changes in feeding were seen after the administration of Agrp into the Arc, LHA, or VMN, but NDP-MSH suppressed food intake in the Arc and LHA [4].
  • Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signaling [5].
  • The ratio of hypothalamic Pomc to Agrp mRNA was elevated two-fold in ad libitum and pair-fed AGRP-injected rats, which is consistent with increased stimulation of central melanocortin signalling pathways [1].

Biological context of Agrp

  • Agrp (83-132) (1 nmol) administered ICV did not block the anorectic effects of CART (55-102) (1 h food intake, 0.2 nmol CART (55-102), 2.7+/-0.8 g vs. CART (55-102)+Agrp (83-132), 2.6+/-0.6 g, P=0.87; saline control 5.4+/-0.3 g, P<0.001 vs. both groups) [6].
  • Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure [2].
  • CONCLUSION: Chronic CNS administration of Agrp decreases oxygen consumption and decreases the capacity of BAT to expend energy [2].

Anatomical context of Agrp


Associations of Agrp with chemical compounds

  • In the first (choice) paradigm, Agrp only increased intake of the sucrose-containing diet [10].
  • An 8% decrease in VO(2) measurements was observed following ICV Agrp treatment on day 1 [2].

Other interactions of Agrp

  • Neuropeptide Y (NPY) and agouti-related protein (Agrp) are orexigenic [11].
  • Agouti-related protein (Agrp) is an endogenous melanocortin-4 receptor antagonist implicated in the regulation of food intake [7].
  • Agrp (83-132) also did not block the anorectic effects of GLP-1 or CRF (1 h food intake, 0.3 nmol CRF, 0.7+/-0.3 g vs. CRF+Agrp (83-132), 0.7+/-0.3 g, P=0.91; 3 nmol GLP-1, 1.9+/-0.4 g vs. GLP-1+Agrp (83-132), 1.1+/-0. 5 g, P=0.23; saline control 5.0+/-0.6 g, P<0.001 vs. all four groups) [6].
  • Inhibitory effects of Agrp on acquisition of CTA and aversion-associated activation of oxytocin neurons parallel what has previously been shown with opioid receptor agonists [8].
  • OBJECTIVE: To investigate whether the Agouti-related protein (Agrp), the melanocortin receptor antagonist, alters oxygen consumption, as a measure of energy expenditure [2].

Analytical, diagnostic and therapeutic context of Agrp

  • At 8 h postinjection, Agrp increased feeding in the PVN by 218 +/- 23% (P < 0.005), in the DMN by 268 +/- 42% (P < 0.005), and in the MPO by 236 +/- 31% (P < 0.01) compared with a saline control group for each nucleus [4].
  • Following exposure to the two diets, rats were injected via cannula aimed at the DMH with 100 pmol Agrp at 10:00 h and allowed ad libitum access to either: (1) a choice of both diets or (2) one of the diets alone [10].


  1. Effects of agouti-related protein on metabolism and hypothalamic neuropeptide gene expression. Korner, J., Wissig, S., Kim, A., Conwell, I.M., Wardlaw, S.L. J. Neuroendocrinol. (2003) [Pubmed]
  2. Chronic CNS administration of Agouti-related protein (Agrp) reduces energy expenditure. Small, C.J., Liu, Y.L., Stanley, S.A., Connoley, I.P., Kennedy, A., Stock, M.J., Bloom, S.R. Int. J. Obes. Relat. Metab. Disord. (2003) [Pubmed]
  3. The central melanocortin system affects the hypothalamo-pituitary thyroid axis and may mediate the effect of leptin. Kim, M.S., Small, C.J., Stanley, S.A., Morgan, D.G., Seal, L.J., Kong, W.M., Edwards, C.M., Abusnana, S., Sunter, D., Ghatei, M.A., Bloom, S.R. J. Clin. Invest. (2000) [Pubmed]
  4. Hypothalamic localization of the feeding effect of agouti-related peptide and alpha-melanocyte-stimulating hormone. Kim, M.S., Rossi, M., Abusnana, S., Sunter, D., Morgan, D.G., Small, C.J., Edwards, C.M., Heath, M.M., Stanley, S.A., Seal, L.J., Bhatti, J.R., Smith, D.M., Ghatei, M.A., Bloom, S.R. Diabetes (2000) [Pubmed]
  5. Leptin inhibits hypothalamic Npy and Agrp gene expression via a mechanism that requires phosphatidylinositol 3-OH-kinase signaling. Morrison, C.D., Morton, G.J., Niswender, K.D., Gelling, R.W., Schwartz, M.W. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  6. Cocaine- and amphetamine-regulated transcript, glucagon-like peptide-1 and corticotrophin releasing factor inhibit feeding via agouti-related protein independent pathways in the rat. Edwards, C.M., Abbott, C.R., Sunter, D., Kim, M., Dakin, C.L., Murphy, K.G., Abusnana, S., Taheri, S., Rossi, M., Bloom, S.R. Brain Res. (2000) [Pubmed]
  7. Agouti-related protein in the hypothalamic paraventricular nucleus: effect on feeding. Wirth, M.M., Giraudo, S.Q. Peptides (2000) [Pubmed]
  8. Effect of Agouti-related protein on development of conditioned taste aversion and oxytocin neuronal activation. Wirth, M.M., Olszewski, P.K., Levine, A.S., Giraudo, S.Q. Neuroreport (2002) [Pubmed]
  9. The hypothalamic melanocortin system stimulates the hypothalamo-pituitary-adrenal axis in vitro and in vivo in male rats. Dhillo, W.S., Small, C.J., Seal, L.J., Kim, M.S., Stanley, S.A., Murphy, K.G., Ghatei, M.A., Bloom, S.R. Neuroendocrinology (2002) [Pubmed]
  10. Effect of Agouti-related protein delivered to the dorsomedial nucleus of the hypothalamus on intake of a preferred versus a non-preferred diet. Wirth, M.M., Giraudo, S.Q. Brain Res. (2001) [Pubmed]
  11. Hypothalamic interactions between neuropeptide Y, agouti-related protein, cocaine- and amphetamine-regulated transcript and alpha-melanocyte-stimulating hormone in vitro in male rats. Dhillo, W.S., Small, C.J., Stanley, S.A., Jethwa, P.H., Seal, L.J., Murphy, K.G., Ghatei, M.A., Bloom, S.R. J. Neuroendocrinol. (2002) [Pubmed]
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