Peptide YY

Peptide YY
PDB rendering based on 1qbf.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2DEZ​, 2DF0​, 2L60​
Identifiers
Symbols	PYY ; PYY-I; PYY1
External IDs	OMIM: 600781 MGI: 99924 HomoloGene: 3066 GeneCards: PYY Gene
Gene ontology Molecular function • G-protein coupled receptor binding • hormone activity • neuropeptide hormone activity • protein binding Cellular component • extracellular region • extracellular space Biological process • movement of cell or subcellular component • cytoskeleton organization • G-protein coupled receptor signaling pathway • neuropeptide signaling pathway • cell-cell signaling • digestion • feeding behavior • cell proliferation • regulation of appetite • eating behavior Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	5697	217212
Ensembl	ENSG00000131096	ENSMUSG00000017311
UniProt	P10082	Q9EPS2
RefSeq (mRNA)	NM_004160	NM_145435
RefSeq (protein)	NP_004151	NP_663410
Location (UCSC)	Chr 17: 43.95 – 44 Mb	Chr 11: 102.11 – 102.11 Mb
PubMed search

Peptide YY (PYY) also known as peptide tyrosine tyrosine or pancreatic peptide YY_3-36 is a peptide that in humans is encoded by the PYY gene.^[1] Peptide YY is a short (36-amino acid) peptide released by cells in the ileum and colon in response to feeding. In the blood, gut, and other elements of periphery, PYY acts to reduce appetite; but when injected directly into the central nervous system, PYY is anorexigenic, i.e., it decreases appetite.^[2]

Peptide YY can be produced as the result of enzymatic breakdown of crude fish proteins and ingested as a food product.^[3]

Structure

Peptide YY is related to the pancreatic peptide family by having 18 of its 36 amino acids located in the same positions as pancreatic peptide.^[4] The two major forms of peptide YY are PYY_1-36 and PYY_3-36, which have PP fold structural motifs. However, the most common form of circulating PYY immunoreactivity is PYY_3-36, which binds to the Y2 receptor (Y2R) of the Y family of receptors.^[5] Peptide YY_3-36 (PYY) is a linear polypeptide consisting of 36 amino acids with structural homology to NPY and pancreatic polypeptide.

Release

PYY is found in L cells in the mucosa of gastrointestinal tract, especially in ileum and colon. Also, a small amount of PYY, about 1-10%, is found in the esophagus, stomach, duodenum and jejunum.^[6] PYY concentration in the circulation increases postprandially (after food ingestion) and decreases by fasting.^[5] In addition, PYY is produced by a discrete population of neurons in the brainstem, specifically localized to the gigantocellular reticular nucleus of the medulla oblongata.^[7] C. R. Gustavsen et al. had found PYY-producing cells located in the islets of Langerhans in rats. They were observed either alone or co-localized with glucagon or PP.^[8]

Function

PYY exerts its action through NPY receptors; it inhibits gastric motility and increases water and electrolyte absorption in the colon.^[9] PYY may also suppress pancreatic secretion. It is secreted by the neuroendocrine cells in the ileum and colon in response to a meal, and has been shown to reduce appetite. PYY works by slowing the gastric emptying; hence, it increases efficiency of digestion and nutrient absorption after a meal. Research has also indicated PYY may be useful in removing aluminium accumulated in the brain.

Animal studies

Several studies have shown acute peripheral administration of PYY_3-36 inhibits feeding of rodents and primates. Other studies on Y2R-knockout mice have shown no anorectic effect on them. These findings indicate PYY_3-36 has an anorectic (losing appetite) effect, which is suggested to be mediated by Y2R. PYY-knockout female mice increase in body weight and fat mass. PYY-knockout mice, on the other hand, are resistant to obesity, but have higher fat mass and lower glucose tolerance when fed a high-fat diet, compared to control mice. Thus, PYY also plays a very important role in energy homeostasis by balancing food intake.^[5] PYY oral spray was found to promote fullness.^[10] Viral gene therapy of the salivary glands resulted in long-term intake reduction.^[11]

Relevance to obesity

Leptin also reduces appetite in response to feeding, but obese people develop a resistance to leptin. Obese people secrete less PYY than non-obese people,^[12] and attempts to use PYY directly as a weight-loss drug have met with some success. Researchers noted the caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30% in obese subjects (P<0.001) and 31% in lean subjects (P<0.001).^[13]

While some studies have shown obese persons have lower circulating level of PYY postprandially, other studies have reported they have normal sensitivity to the anorectic effect of PYY_3-36. Thus, reduction in PYY sensitivity may not be one of the causes of obesity, in contrast to the reduction of leptin sensitivity. The anorectic effect of PYY could possibly be a future obesity drug.^[5]

The consumption of protein boosts PYY levels, so some benefit was observed in experimental subjects in reducing hunger and promoting weight loss.^[14] This would help explain the weight-loss experienced with high-protein diets.

Obese patients undergoing gastric bypass showed marked metabolic adaptations, resulting in frequent diabetes remission 1 year later. When the confounding of calorie restriction is factored out, β-cell function improves rapidly, very possibly under the influence of enhanced GLP-1 responsiveness. Insulin sensitivity improves in proportion to weight loss, with a possible involvement of PYY.^[15]

See also

• Ghrelin
• Leptin

References

1. EntrezGene 5697
2. Woods S. C., D'Alessio D. A. (2008). "Central control of body weight and appetite". J Clin Endocrinol Metab 93 (11 Suppl 1): S37–50. doi:10.1210/jc.2008-1630.
3. http://www.bio.umass.edu/biology/mccormick/pdf/Murashita%20et%20al%202009.pdf
4. DeGroot, Leslie Jacob (1989). J. E. McGuigan, ed. Endocrinology. Philadelphia: Saunders. p. 2754. ISBN 0-7216-2888-5.
5. Murphy KG, Bloom SR (December 2006). "Gut hormones and the regulation of energy homeostasis". Nature 444 (7121): 854–9. doi:10.1038/nature05484. PMID 17167473.
6. Taylor IL (March 1985). "Distribution and release of peptide YY in dog measured by specific radioimmunoassay". Gastroenterology 88 (3): 731–7. PMID 3838162.
7. Glavas MM, Grayson BE, Allen SE, Copp DR, Smith MS, Cowley MA, Grove KL (2008). "Characterization of brainstem peptide YY (PYY) neurons". J Comp Neurol 506 (2): 194–210. doi:10.1002/cne.21543. PMID 18022952.
8. Gustavsen CR, Pillay N, Heller RS (2008). "An immunohistochemical study of the endocrine pancreas of the African ice rat, Otomys sloggetti robertsi". Acta Histochem. 110 (4): 294–301. doi:10.1016/j.acthis.2007.11.003. PMID 18406449.
9. Liu C, Aloia T, Adrian T, Newton T, Bilchik A, Zinner M, Ashley S, McFadden D (1996). "Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders". Am Surg 62 (3): 232–6. PMID 8607584.
10. "UF researchers use oral peptide spray to stimulate weight loss in animals". Dec 19, 2013.
11. "Salivary PYY: a putative bypass to satiety.". PLOS ONE 6: e26137. 2011. doi:10.1371/journal.pone.0026137. PMID 22028819.
12. Alvarez Bartolomé M, Borque M, Martinez-Sarmiento J, Aparicio E, Hernández C, Cabrerizo L, Fernández-Represa JA (June 2002). "Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty". Obes Surg 12 (3): 324–7. doi:10.1381/096089202321088084. PMID 12082881.
13. Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR (September 2003). "Inhibition of food intake in obese subjects by peptide YY3-36". The New England Journal of Medicine 349 (10): 941–8. doi:10.1056/NEJMoa030204. PMID 12954742.
14. Batterham RL, Heffron H, Kapoor S, Chivers J, Chandarana K, Herzog H, Le Roux CW, Thomas EL, Bell JD, Withers DJ (2006). "Critical role for peptide YY in protein-mediated satiation and body-weight regulation". Cell Metabolism 4 (3): 223–233. doi:10.1016/j.cmet.2006.08.001. PMID 16950139.
15. Nannipieri M, Baldi S, Mari A, Colligiani D, Guarino D, Camastra S, Barsotti E, Berta R, Moriconi D, Bellini R, Anselmino M, Ferrannini E (November 2013). "Roux-en-Y Gastric Bypass and Sleeve Gastrectomy: Mechanisms of Diabetes Remission and Role of Gut Hormones". J. Clin. Endocrinol. Metab. 98 (11): 4391–9. doi:10.1210/jc.2013-2538. PMID 24057293.

Further reading

• Ekblad E, Sundler F (2002). "Distribution of pancreatic polypeptide and peptide YY". Peptides 23 (2): 251–61. doi:10.1016/S0196-9781(01)00601-5. PMID 11825640.
• Sandström O, El-Salhy M (2002). "Ontogeny and the effect of aging on pancreatic polypeptide and peptide YY". Peptides 23 (2): 263–7. doi:10.1016/S0196-9781(01)00603-9. PMID 11825641.
• Yang H (2002). "Central and peripheral regulation of gastric acid secretion by peptide YY". Peptides 23 (2): 349–58. doi:10.1016/S0196-9781(01)00611-8. PMID 11825649.
• Naruse S, Kitagawa M, Ishiguro H, Hayakawa T (2002). "Feedback regulation of pancreatic secretion by peptide YY". Peptides 23 (2): 359–65. doi:10.1016/S0196-9781(01)00612-X. PMID 11825650.
• Aponte GW (2002). "PYY-mediated fatty acid induced intestinal differentiation". Peptides 23 (2): 367–76. doi:10.1016/S0196-9781(01)00613-1. PMID 11825651.
• Hagan MM (2002). "Peptide YY: a key mediator of orexigenic behavior". Peptides 23 (2): 377–82. doi:10.1016/S0196-9781(01)00614-3. PMID 11825652.
• Mannon PJ (2002). "Peptide YY as a growth factor for intestinal epithelium". Peptides 23 (2): 383–8. doi:10.1016/S0196-9781(01)00615-5. PMID 11825653.
• Tseng WW, Liu CD (2002). "Peptide YY and cancer: current findings and potential clinical applications". Peptides 23 (2): 389–95. doi:10.1016/S0196-9781(01)00616-7. PMID 11825654.
• El-Salhy M, Suhr O, Danielsson A (2002). "Peptide YY in gastrointestinal disorders". Peptides 23 (2): 397–402. doi:10.1016/S0196-9781(01)00617-9. PMID 11825655.
• Imamura M (2002). "Effects of surgical manipulation of the intestine on peptide YY and its physiology". Peptides 23 (2): 403–7. doi:10.1016/S0196-9781(01)00618-0. PMID 11825656.
• Beglinger C, Degen L (2007). "Gastrointestinal satiety signals in humans--physiologic roles for GLP-1 and PYY?". Physiol. Behav. 89 (4): 460–4. doi:10.1016/j.physbeh.2006.05.048. PMID 16828127.
• Eberlein GA, Eysselein VE, Schaeffer M, Layer P, Grandt D, Goebell H, Niebel W, Davis M, Lee TD, Shively JE, et al. (1989). "A new molecular form of PYY: structural characterization of human PYY(3-36) and PYY(1-36)". Peptides 10 (4): 797–803. doi:10.1016/0196-9781(89)90116-2. PMID 2587421.
• Facer P, Bishop AE, Cole GA, Aitchison M, Kendall CH, van Aswegen G, Penketh RJ, Rodek CH, McKeever P, Polak JM (1989). "Developmental profile of chromogranin, hormonal peptides, and 5-hydroxytryptamine in gastrointestinal endocrine cells". Gastroenterology 97 (1): 48–57. PMID 2721879.
• Tatemoto K, Nakano I, Makk G, Angwin P, Mann M, Schilling J, Go VL (1989). "Isolation and primary structure of human peptide YY". Biochem. Biophys. Res. Commun. 157 (2): 713–7. doi:10.1016/S0006-291X(88)80308-5. PMID 3202875.
• Lukinius AI, Ericsson JL, Lundqvist MK, Wilander EM (1986). "Ultrastructural localization of serotonin and polypeptide YY (PYY) in endocrine cells of the human rectum". J. Histochem. Cytochem. 34 (6): 719–26. doi:10.1177/34.6.3517149. PMID 3517149.
• Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR (1985). "Human distribution and release of a putative new gut hormone, peptide YY". Gastroenterology 89 (5): 1070–7. PMID 3840109.
• Lundell I, Blomqvist AG, Berglund MM, Schober DA, Johnson D, Statnick MA, Gadski RA, Gehlert DR, Larhammar D (1996). "Cloning of a human receptor of the NPY receptor family with high affinity for pancreatic polypeptide and peptide YY". J. Biol. Chem. 270 (49): 29123–8. doi:10.1074/jbc.270.49.29123. PMID 7493937.
• Bard JA, Walker MW, Branchek TA, Weinshank RL (1995). "Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY". J. Biol. Chem. 270 (45): 26762–5. doi:10.1074/jbc.270.45.26762. PMID 7592911.
• Hort Y, Baker E, Sutherland GR, Shine J, Herzog H (1995). "Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1". Genomics 26 (1): 77–83. doi:10.1016/0888-7543(95)80085-Z. PMID 7782089.
• Kohri K, Nata K, Yonekura H, Nagai A, Konno K, Okamoto H (1993). "Cloning and structural determination of human peptide YY cDNA and gene". Biochim. Biophys. Acta 1173 (3): 345–9. doi:10.1016/0167-4781(93)90136-2. PMID 8318545.

External links

• Peptide YY at the US National Library of Medicine Medical Subject Headings (MeSH)