Agouti-related peptide
AGRP | |||
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Gene ontology | |||
Molecular function | |||
Cellular component | |||
Biological process |
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Sources:Amigo / QuickGO |
Ensembl | |||||||||
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UniProt | |||||||||
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RefSeq (protein) | |||||||||
Location (UCSC) | Chr 16: 67.48 – 67.48 Mb | Chr 8: 106.29 – 106.36 Mb | |||||||
PubMed search | [3] | [4] |
View/Edit Human | View/Edit Mouse |
Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus.[5] AgRP is co-expressed with NPY and acts to increase appetite and decrease metabolism and energy expenditure. It is one of the most potent and long-lasting of appetite stimulators. In humans, the agouti-related peptide is encoded by the AGRP gene.[6][7]
Structure
AgRP is a paracrine signaling molecule made of 112 amino acids (the gene product of 132 amino acids is processed by removal of the N-terminal 20-residue signal peptide domain). It was independently identified by two teams in 1997 based on its sequence similarity with
Function
Agouti-related protein is expressed primarily in the adrenal gland, subthalamic nucleus, and hypothalamus, with lower levels of expression in the testis, kidneys, and lungs. The appetite-stimulating effects of AgRP are inhibited by the hormone
Mechanism
AGRP has been demonstrated to be a competitive antagonist of
History
Role in obesity
AgRP induces obesity by chronic antagonism of the MC4-R.
Agouti protein | |||||||||
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OPM superfamily | 112 | ||||||||
OPM protein | 1mr0 | ||||||||
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Role in hunger circuitry
According to Mark L. Andermann and Bradford B. Lowell: "...AgRP neurons and the wiring diagram within which they operate can be viewed as the physical embodiment of the intervening variable, hunger."[24] Stimulation of neurons expressing AgRP can induce robust feeding behavior in mice that will trigger: increased food consumption,[25] increased willingness to work for food,[26] and increased investigation of food odors.[27]
Despite this, AgRP neurons are rapidly inhibited upon food presentation and the onset of eating.[28] One mechanism which may account for this discrepancy is the fact that AgRP neurons signal with Neuropeptide Y in order to allow for sustained feeding behavior that outlasts the activation of the neurons.[29]
AgRP neurons are also sensitive to satiety and hunger hormonal signals. One is an appetite stimulant, ghrelin which makes AgRP neurons more excitable through interactions with specialized ghrelin receptors.[30] Another is a satiety signal, leptin, which modulates AgRP activity through inwardly rectifying potassium channels, which alter the excitability of the neurons.[31] Leptin can also decrease the ability of AgRP neurons to carry out other physiological functions, such as triggering Long Term Potentiation of adjacent neurons.[32]
Although AgRP neurons can drive many different phases of feeding behavior, separate AgRP neurons project to different areas of the brain, demonstrating a parallel organizational structure.[33] This is evidenced by different projections of AgRP neurons to various areas of the brain driving different food related behaviors; for example, certain projections will promote increased food consumption, but not increased food odor investigation.[27]
Human proteins containing this domain
AGRP;
See also
- Proopiomelanocortin
- Agouti (gene)
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000159723 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000005705 - Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- PMID 15193430.
- ^ PMID 9119224.
- ^ PMID 9311920.
- PMID 9819197.
- PMID 12056887.
- PMID 17339026.
- PMID 16384863.
- PMID 18583425.
- PMID 12697678.
- PMID 20074584.
- PMID 24487620.
- ^ PMID 17185225.
- PMID 9450927.
- PMID 12535647.
- S2CID 14528879.
- S2CID 36127101.
- PMID 11344185.
- S2CID 6755288.
- PMID 21803288.
- PMID 28817798.
- PMID 21209617.
- PMID 21364278.
- ^ PMID 33658716.
- PMID 25703096.
- PMID 31033437.
- PMID 24567905.
- PMID 24741039.
- PMID 33414382.
- PMID 24315102.
Further reading
- Dhillo WS, Gardiner JV, Castle L, Bewick GA, Smith KL, Meeran K, et al. (December 2005). "Agouti related protein (AgRP) is upregulated in Cushing's syndrome". Experimental and Clinical Endocrinology & Diabetes. 113 (10): 602–6. PMID 16320160.
- Dinulescu DM, Cone RD (March 2000). "Agouti and agouti-related protein: analogies and contrasts". The Journal of Biological Chemistry. 275 (10): 6695–8. PMID 10702221.
- Scarlett JM, Zhu X, Enriori PJ, Bowe DD, Batra AK, Levasseur PR, et al. (October 2008). "Regulation of agouti-related protein messenger ribonucleic acid transcription and peptide secretion by acute and chronic inflammation". Endocrinology. 149 (10): 4837–45. PMID 18583425.
- Creemers JW, Pritchard LE, Gyte A, Le Rouzic P, Meulemans S, Wardlaw SL, et al. (April 2006). "Agouti-related protein is posttranslationally cleaved by proprotein convertase 1 to generate agouti-related protein (AGRP)83-132: interaction between AGRP83-132 and melanocortin receptors cannot be influenced by syndecan-3". Endocrinology. 147 (4): 1621–31. PMID 16384863.
- Katsuki A, Sumida Y, Gabazza EC, Murashima S, Tanaka T, Furuta M, et al. (May 2001). "Plasma levels of agouti-related protein are increased in obese men". The Journal of Clinical Endocrinology and Metabolism. 86 (5): 1921–4. PMID 11344185.
- Kas MJ, Bruijnzeel AW, Haanstra JR, Wiegant VM, Adan RA (August 2005). "Differential regulation of agouti-related protein and neuropeptide Y in hypothalamic neurons following a stressful event". Journal of Molecular Endocrinology. 35 (1): 159–64. PMID 16087729.
- Jackson PJ, Yu B, Hunrichs B, Thompson DA, Chai B, Gantz I, Millhauser GL (October 2005). "Chimeras of the agouti-related protein: insights into agonist and antagonist selectivity of melanocortin receptors". Peptides. 26 (10): 1978–87. S2CID 45039327.
- Bäckberg M, Madjid N, Ogren SO, Meister B (June 2004). "Down-regulated expression of agouti-related protein (AGRP) mRNA in the hypothalamic arcuate nucleus of hyperphagic and obese tub/tub mice". Brain Research. Molecular Brain Research. 125 (1–2): 129–39. PMID 15193430.
External links
- agouti-related+protein at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Agouti domain[permanent dead link] in PROSITE
- Human AGRP genome location and AGRP gene details page in the UCSC Genome Browser.