Peptide YY

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

Dietary fibers from fruits, vegetables, and whole grains, consumed, increase the speed of transit of intestinal chyme into the ileum, to raise PYY3-36, and induce satiety. 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 PYY1-36 and PYY3-36, which have PP fold structural motifs. However, the most common form of circulating PYY immunoreactivity is PYY3-36, which binds to the Y2 receptor (Y2R) of the Y family of receptors.[5] Peptide YY3-36 (PYY) is a linear polypeptide consisting of 34 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.[citation needed]

Animal studies

Several studies have shown acute peripheral administration of PYY3-36 inhibits feeding of rodents and primates. Other studies on Y2R-knockout mice have shown no anorectic effect on them. These findings indicate PYY3-36 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 PYY3-36. 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 could partially explain the weight-loss experienced with high-protein diets, but the high thermic effect of protein appears to be the leading cause.

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

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. PMC 2585760. PMID 18987269.
  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. 5.0 5.1 5.2 5.3 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. Acosta A, Hurtado MD, Gorbatyuk O, La Sala M, Duncan D, Aslanidi G, Campbell-Thompson M, Zhang L, Herzog H, Voutetakis A, Baum BJ, Zolotukhin S (2011). "Salivary PYY: a putative bypass to satiety". PLOS ONE. 6 (10): e26137. doi:10.1371/journal.pone.0026137. PMC 3189958. 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.

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