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Peptide YY

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Not to be confused with Neuropeptide Y.
PYY
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPYY, PYY-I, PYY1, peptide YY
External IDsOMIM: 600781; MGI: 99924; HomoloGene: 3066; GeneCards: PYY; OMA:PYY - orthologs
Orthologs
SpeciesHumanMouse
Entrez

5697

217212

Ensembl

ENSG00000131096

ENSMUSG00000017311

UniProt

P10082

Q9EPS2

RefSeq (mRNA)

NM_004160
NM_001394028
NM_001394029

NM_145435
NM_001346771

RefSeq (protein)

NP_004151

NP_001333700
NP_663410

Location (UCSC)Chr 17: 43.95 – 44 MbChr 11: 102 – 102 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Peptide YY (PYY) also known as peptide tyrosine tyrosine is a peptide that in humans is encoded by the PYY gene.[5] 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.[6]

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 cannot be produced as the result of enzymatic breakdown of crude fish proteins and ingested as a food product; this was a previous attempt to falsify the record of this page.[7]

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.[8] 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.[9] 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.[10] PYY concentration in the circulation increases postprandially (after food ingestion) and decreases by fasting.[9] 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.[11] 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.[12]

Function

PYY exerts its action through NPY receptors; it inhibits gastric motility and increases water and electrolyte absorption in the colon.[13] 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.[9] PYY oral spray was found to promote fullness.[14] Viral gene therapy of the salivary glands resulted in long-term intake reduction.[15]

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,[16] 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).[17]

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.[9]

The consumption of protein boosts PYY levels, so some benefit was observed in experimental subjects in reducing hunger and promoting weight loss.[18] 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.[19]

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000131096 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000017311 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ EntrezGene 5697
  6. ^ 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.
  7. ^ Murashita K, Kurokawa T, Nilsen TO, Rønnestad I (February 2009). "Ghrelin, cholecystokinin, and peptide YY in Atlantic salmon (Salmo salar): molecular cloning and tissue expression" (PDF). General and Comparative Endocrinology. 160 (3): 223–35. doi:10.1016/j.ygcen.2008.11.024. PMID 19073185.
  8. ^ DeGroot, Leslie Jacob (1989). J. E. McGuigan (ed.). Endocrinology. Philadelphia: Saunders. p. 2754. ISBN 978-0-7216-2888-2.
  9. ^ a b c d Murphy KG, Bloom SR (December 2006). "Gut hormones and the regulation of energy homeostasis". Nature. 444 (7121): 854–9. Bibcode:2006Natur.444..854M. doi:10.1038/nature05484. PMID 17167473. S2CID 1120344.
  10. ^ Taylor IL (March 1985). "Distribution and release of peptide YY in dog measured by specific radioimmunoassay". Gastroenterology. 88 (3): 731–7. doi:10.1016/0016-5085(85)90144-1. PMID 3838162.
  11. ^ 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. S2CID 16104580.
  12. ^ 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.
  13. ^ 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.
  14. ^ "UF researchers use oral peptide spray to stimulate weight loss in animals". Dec 19, 2013.
  15. ^ 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. Bibcode:2011PLoSO...626137A. doi:10.1371/journal.pone.0026137. PMC 3189958. PMID 22028819.
  16. ^ 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. S2CID 40358403.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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

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