PYY
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesPYY, PYY-I, PYY1, peptide YY
External IDsOMIM: 600781 MGI: 99924 HomoloGene: 3066 GeneCards: PYY
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.[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.

The PP-fold motif is found throughout this family and relates to the 3D structure. The PP-fold is formed through the incorporation of certain residues which are predominately Pro2, Pro5, Pro8, Gly9, Tyr20 and Tyr27. This PP-fold has been found to protect the peptide against enzymatic attack as well as producing a hydrophobic pocket which is inherently overall energy reducing. In addition to containing the PP-fold motif, PYY and its derivative PYY3- 36 also have a high C-terminal α-helix proportion, suggested to be extremely important for the structural integrity of PYY.[10]

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.[11] 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.[12] 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.[13]

PYY is released by the L-cells of the gastrointestinal tract following food intake, and there are two main endogenous forms: PYY1-36 and PYY3-36. PYY1-36 is rapidly processed by the enzyme DPP4 to the 34-amino acid peptide PYY3-36.<[14] DPP4 hydrolyses PYY and removes the first two amino acids, tyrosine and proline, at the N-terminal, which changes the receptor selectivity. As a result of this, PYY3-36 has a high selectivity for the Y2-receptor, compared to PYY1-36 which has selectivity for the Y1, Y2, and Y5 receptors. It is thought that the Y1 receptor requires both the C-terminus and N-terminus for recognition, binding and then subsequent activation. The Y2 receptor is thought to have a smaller receptor site and also only requires the C-terminus for recognition.

This could explain the reduced affinity for PYY3-36 on any other Y receptor other than Y2.[15] Other studies replacing the amide bonds with ester bonds also confirm that the end section is important in binding and activation.[16] The Y2 receptors are located in the hippocampus, sympathetic and parasympathetic nerve fibres, intestines, and certain blood vessels, and have been implicated in regulating food intake and gastric emptying.[17] As a result of this, the Y2 receptor is considered a target for the treatment of obesity and type II diabetes.

Function

PYY exerts its action through NPY receptors; it inhibits gastric motility and increases water and electrolyte absorption in the colon.[18] 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 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.[19] Viral gene therapy of the salivary glands resulted in long-term intake reduction.[20]

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,[21] 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).[22]

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.[23] This could partially explain the weight-loss experienced with high-protein diets, noting also the high thermic effect of protein.

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.[24]

See also

References

 This article incorporates text by Jessica Hutchinson available under the CC BY 3.0 license.

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000131096 - Ensembl, May 2017
  2. 1 2 3 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 SC, D'Alessio DA (November 2008). "Central control of body weight and appetite". The Journal of Clinical Endocrinology and Metabolism. 93 (11 Suppl 1): S37–S50. 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". General and Comparative Endocrinology. 160 (3): 223–235. doi:10.1016/j.ygcen.2008.11.024. PMID 19073185.
  8. ↑ DeGroot LJ (1989). McGuigan JE (ed.). Endocrinology. Philadelphia: Saunders. p. 2754. ISBN 978-0-7216-2888-2.
  9. 1 2 3 4 Murphy KG, Bloom SR (December 2006). "Gut hormones and the regulation of energy homeostasis". Nature. 444 (7121): 854–859. Bibcode:2006Natur.444..854M. doi:10.1038/nature05484. PMID 17167473. S2CID 1120344.
  10. ↑ Tatemoto K (April 1982). "Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine secretion". Proceedings of the National Academy of Sciences of the United States of America. 79 (8): 2514–8. Bibcode:1982PNAS...79.2514T. doi:10.1073/pnas.79.8.2514. PMC 346229. PMID 6953409.
  11. ↑ Taylor IL (March 1985). "Distribution and release of peptide YY in dog measured by specific radioimmunoassay". Gastroenterology. 88 (3): 731–737. doi:10.1016/0016-5085(85)90144-1. PMID 3838162.
  12. ↑ Glavas MM, Grayson BE, Allen SE, Copp DR, Smith MS, Cowley MA, Grove KL (January 2008). "Characterization of brainstem peptide YY (PYY) neurons". The Journal of Comparative Neurology. 506 (2): 194–210. doi:10.1002/cne.21543. PMID 18022952. S2CID 16104580.
  13. ↑ Gustavsen CR, Pillay N, Heller RS (2008). "An immunohistochemical study of the endocrine pancreas of the African ice rat, Otomys sloggetti robertsi". Acta Histochemica. 110 (4): 294–301. doi:10.1016/j.acthis.2007.11.003. PMID 18406449.
  14. ↑ Ehrlich GK, Michel H, Truitt T, Riboulet W, Pop-Damkov P, Goelzer P, Hainzl D, Qureshi F, Lueckel B, Danho W, Conde-Knape K, Konkar A (December 2013). "Preparation and characterization of albumin conjugates of a truncated peptide YY analogue for half-life extension". Bioconjugate Chemistry. 24 (12): 2015–24. doi:10.1021/bc400340z. PMID 24251972.
  15. ↑ Nygaard R, Nielbo S, Schwartz TW, Poulsen FM (July 2006). "The PP-fold solution structure of human polypeptide YY and human PYY3-36 as determined by NMR". Biochemistry. 45 (27): 8350–7. doi:10.1021/bi060359l. PMID 16819834.
  16. ↑ Albertsen L, Andersen JJ, Paulsson JF, Thomsen JK, Norrild JC, Strømgaard K (December 2013). "Design and Synthesis of Peptide YY Analogues with C-terminal Backbone Amide-to-Ester Modifications". ACS Medicinal Chemistry Letters. 4 (12): 1228–32. doi:10.1021/ml400335g. PMC 4027376. PMID 24900634.
  17. ↑ Keire DA, Bowers CW, Solomon TE, Reeve JR (February 2002). "Structure and receptor binding of PYY analogs". Peptides. 23 (2): 305–21. doi:10.1016/s0196-9781(01)00602-7. PMID 11825645. S2CID 7082920.
  18. ↑ Liu CD, Aloia T, Adrian TE, Newton TR, Bilchik AJ, Zinner MJ, et al. (March 1996). "Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders". The American Surgeon. 62 (3): 232–236. PMID 8607584.
  19. ↑ "UF researchers use oral peptide spray to stimulate weight loss in animals". Dec 19, 2013.
  20. ↑ Acosta A, Hurtado MD, Gorbatyuk O, La Sala M, Duncan D, Aslanidi G, et al. (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.
  21. ↑ 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". Obesity Surgery. 12 (3): 324–327. doi:10.1381/096089202321088084. PMID 12082881. S2CID 40358403.
  22. ↑ Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, et al. (September 2003). "Inhibition of food intake in obese subjects by peptide YY3-36". The New England Journal of Medicine. 349 (10): 941–948. doi:10.1056/NEJMoa030204. PMID 12954742. S2CID 11764433.
  23. ↑ Batterham RL, Heffron H, Kapoor S, Chivers JE, Chandarana K, Herzog H, et al. (September 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.
  24. ↑ Nannipieri M, Baldi S, Mari A, Colligiani D, Guarino D, Camastra S, et al. (November 2013). "Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones". The Journal of Clinical Endocrinology and Metabolism. 98 (11): 4391–4399. doi:10.1210/jc.2013-2538. PMID 24057293.

Further reading

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