{{Short description|Peptide released from cells in the ileum and colon in response to feeding}} {{Distinguish|Neuropeptide Y|Pancreatic polypeptide}} {{Redirect|PYY|the IATA code PYY|Pai Airport}} {{Infobox gene}} '''Peptide YY''' ('''PYY'''), also known as '''peptide tyrosine tyrosine''', is a peptide that in humans is encoded by the {{gene|PYY}} gene.<ref name="entrez">{{EntrezGene|5697}}</ref> 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.<ref>{{cite journal | vauthors = Woods SC, D'Alessio DA | title = Central control of body weight and appetite | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 93 | issue = 11 Suppl 1 | pages = S37–S50 | date = November 2008 | pmid = 18987269 | pmc = 2585760 | doi = 10.1210/jc.2008-1630 }}</ref>

Dietary fibers from fruits, vegetables, and whole grains, consumed, increase the speed of transit of intestinal chyme into the ileum, to raise PYY<sub>3-36</sub>, and induce satiety. Peptide YY cannot be produced as the result of enzymatic breakdown of crude fish proteins and ingested as a food product.<ref name="Murashita_2009">{{cite journal | vauthors = Murashita K, Kurokawa T, Nilsen TO, Rønnestad I | title = Ghrelin, cholecystokinin, and peptide YY in Atlantic salmon (Salmo salar): molecular cloning and tissue expression | journal = General and Comparative Endocrinology | volume = 160 | issue = 3 | pages = 223–235 | date = February 2009 | pmid = 19073185 | doi = 10.1016/j.ygcen.2008.11.024 }}</ref>

== 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.<ref name="isbn0-7216-2888-5">{{cite book | vauthors = DeGroot LJ | veditors = McGuigan JE | title = Endocrinology | publisher = Saunders | location = Philadelphia | year = 1989 | isbn = 978-0-7216-2888-2 | url = https://archive.org/details/endocrinology0002unse/page/2754 | page = [https://archive.org/details/endocrinology0002unse/page/2754 2754] }}</ref> The two major forms of peptide YY are PYY<sub>1-36</sub> and PYY<sub>3-36</sub>, which have PP fold structural motifs. However, the most common form of circulating PYY immunoreactivity is PYY<sub>3-36</sub>, which binds to the Y<small>2</small> receptor (Y2R) of the Y family of receptors.<ref name="pmid17167473">{{cite journal | vauthors = Murphy KG, Bloom SR | title = Gut hormones and the regulation of energy homeostasis | journal = Nature | volume = 444 | issue = 7121 | pages = 854–859 | date = December 2006 | pmid = 17167473 | doi = 10.1038/nature05484 | s2cid = 1120344 | bibcode = 2006Natur.444..854M }}</ref> Peptide YY<sub>3-36</sub> (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.<ref name="pmid6953409">{{cite journal | vauthors = Tatemoto K | title = Isolation and characterization of peptide YY (PYY), a candidate gut hormone that inhibits pancreatic exocrine secretion | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 79 | issue = 8 | pages = 2514–8 | date = April 1982 | pmid = 6953409 | pmc = 346229 | doi = 10.1073/pnas.79.8.2514 | bibcode = 1982PNAS...79.2514T | doi-access = free }}</ref>

==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.<ref name="pmid3838162">{{cite journal | vauthors = Taylor IL | title = Distribution and release of peptide YY in dog measured by specific radioimmunoassay | journal = Gastroenterology | volume = 88 | issue = 3 | pages = 731–737 | date = March 1985 | pmid = 3838162 | doi = 10.1016/0016-5085(85)90144-1 }}</ref> PYY concentration in the circulation increases postprandially (after food ingestion) and decreases by fasting.<ref name="pmid17167473"/> 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.<ref>{{cite journal | vauthors = Glavas MM, Grayson BE, Allen SE, Copp DR, Smith MS, Cowley MA, Grove KL | title = Characterization of brainstem peptide YY (PYY) neurons | journal = The Journal of Comparative Neurology | volume = 506 | issue = 2 | pages = 194–210 | date = January 2008 | pmid = 18022952 | doi = 10.1002/cne.21543 | s2cid = 16104580 }}</ref> 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.<ref name="pmid18406449">{{cite journal | vauthors = Gustavsen CR, Pillay N, Heller RS | title = An immunohistochemical study of the endocrine pancreas of the African ice rat, Otomys sloggetti robertsi | journal = Acta Histochemica | volume = 110 | issue = 4 | pages = 294–301 | year = 2008 | pmid = 18406449 | doi = 10.1016/j.acthis.2007.11.003 }}</ref>

PYY is released by the L-cells of the gastrointestinal tract following food intake, and there are two main endogenous forms: PYY<sub>1-36</sub> and PYY<sub>3-36</sub>. PYY<sub>1-36</sub> is rapidly processed by the enzyme DPP4 to the 34-amino acid peptide PYY<sub>3-36.</sub><ref name="pmid24251972">{{cite journal | vauthors = 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 | title = Preparation and characterization of albumin conjugates of a truncated peptide YY analogue for half-life extension | journal = Bioconjugate Chemistry | volume = 24 | issue = 12 | pages = 2015–24 | date = December 2013 | pmid = 24251972 | doi = 10.1021/bc400340z }}</ref> 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, PYY<sub>3-36</sub> has a high selectivity for the Y2-receptor, compared to PYY<sub>1-36</sub> 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 PYY<sub>3-36</sub> on any other Y receptor other than Y2.<ref name="pmid16819834">{{cite journal | vauthors = Nygaard R, Nielbo S, Schwartz TW, Poulsen FM | title = The PP-fold solution structure of human polypeptide YY and human PYY3-36 as determined by NMR | journal = Biochemistry | volume = 45 | issue = 27 | pages = 8350–7 | date = July 2006 | pmid = 16819834 | doi = 10.1021/bi060359l }}</ref> Other studies replacing the amide bonds with ester bonds also confirm that the end section is important in binding and activation.<ref name="pmid24900634">{{cite journal | vauthors = Albertsen L, Andersen JJ, Paulsson JF, Thomsen JK, Norrild JC, Strømgaard K | title = Design and Synthesis of Peptide YY Analogues with C-terminal Backbone Amide-to-Ester Modifications | journal = ACS Medicinal Chemistry Letters | volume = 4 | issue = 12 | pages = 1228–32 | date = December 2013 | pmid = 24900634 | pmc = 4027376 | doi = 10.1021/ml400335g }}</ref> 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.<ref name="pmid11825645">{{cite journal | vauthors = Keire DA, Bowers CW, Solomon TE, Reeve JR | title = Structure and receptor binding of PYY analogs | journal = Peptides | volume = 23 | issue = 2 | pages = 305–21 | date = February 2002 | pmid = 11825645 | doi = 10.1016/s0196-9781(01)00602-7 | s2cid = 7082920 }}</ref> 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.<ref>{{cite journal | vauthors = Liu CD, Aloia T, Adrian TE, Newton TR, Bilchik AJ, Zinner MJ, Ashley SW, McFadden DW | display-authors = 6 | title = Peptide YY: a potential proabsorptive hormone for the treatment of malabsorptive disorders | journal = The American Surgeon | volume = 62 | issue = 3 | pages = 232–236 | date = March 1996 | pmid = 8607584 }}</ref> 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|date=November 2012}}

==Animal studies== Several studies have shown acute peripheral administration of PYY<sub>3-36</sub> inhibits feeding of rodents and primates. Other studies on Y2R-knockout mice have shown no anorectic effect on them. These findings indicate PYY<sub>3-36</sub> 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.<ref name="pmid17167473"/> PYY oral spray was found to promote fullness.<ref>{{Cite news|url = http://news.ufl.edu/archive/2013/12/uf-researchers-use-oral-peptide-spray-to-stimulate-weight-loss-in-animals.html|title = UF researchers use oral peptide spray to stimulate weight loss in animals|date = Dec 19, 2013}}</ref> Viral gene therapy of the salivary glands resulted in long-term intake reduction.<ref>{{cite journal | vauthors = 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 | display-authors = 6 | title = Salivary PYY: a putative bypass to satiety | journal = PLOS ONE | volume = 6 | issue = 10 | article-number = e26137 | date = 2011 | pmid = 22028819 | pmc = 3189958 | doi = 10.1371/journal.pone.0026137 | doi-access = free | bibcode = 2011PLoSO...626137A }}</ref>

==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,<ref name="pmid12082881">{{cite journal | vauthors = Alvarez Bartolomé M, Borque M, Martinez-Sarmiento J, Aparicio E, Hernández C, Cabrerizo L, Fernández-Represa JA | title = Peptide YY secretion in morbidly obese patients before and after vertical banded gastroplasty | journal = Obesity Surgery | volume = 12 | issue = 3 | pages = 324–327 | date = June 2002 | pmid = 12082881 | doi = 10.1381/096089202321088084 | s2cid = 40358403 }}</ref> 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&nbsp;<&nbsp;0.001) and 31% in lean subjects (p&nbsp;<&nbsp;0.001).<ref name="pmid12954742">{{cite journal | vauthors = Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR | display-authors = 6 | title = Inhibition of food intake in obese subjects by peptide YY3-36 | journal = The New England Journal of Medicine | volume = 349 | issue = 10 | pages = 941–948 | date = September 2003 | pmid = 12954742 | doi = 10.1056/NEJMoa030204 | s2cid = 11764433 | url = https://discovery.ucl.ac.uk/id/eprint/8671/ | doi-access = free }}</ref>

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<sub>3-36</sub>. 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.<ref name="pmid17167473"/>

The consumption of protein boosts PYY levels, so some benefit was observed in experimental subjects in reducing hunger and promoting weight loss.<ref>{{cite journal | vauthors = Batterham RL, Heffron H, Kapoor S, Chivers JE, Chandarana K, Herzog H, Le Roux CW, Thomas EL, Bell JD, Withers DJ | display-authors = 6 | title = Critical role for peptide YY in protein-mediated satiation and body-weight regulation | journal = Cell Metabolism | volume = 4 | issue = 3 | pages = 223–233 | date = September 2006 | pmid = 16950139 | doi = 10.1016/j.cmet.2006.08.001 | doi-access = free }}</ref> 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.<ref name="pmid24057293">{{cite journal | vauthors = Nannipieri M, Baldi S, Mari A, Colligiani D, Guarino D, Camastra S, Barsotti E, Berta R, Moriconi D, Bellini R, Anselmino M, Ferrannini E | display-authors = 6 | title = Roux-en-Y gastric bypass and sleeve gastrectomy: mechanisms of diabetes remission and role of gut hormones | journal = The Journal of Clinical Endocrinology and Metabolism | volume = 98 | issue = 11 | pages = 4391–4399 | date = November 2013 | pmid = 24057293 | doi = 10.1210/jc.2013-2538 | doi-access = free }}</ref>

== See also == * Ghrelin * Leptin

== References == {{CC-notice|cc=by3|url=https://en.wikipedia.org/wiki/User_talk:Minihaa/Impact_of_Lipidation|author= Jessica Hutchinson}} {{Reflist|35em}}

== Further reading == {{refbegin|35em}} * {{cite journal | vauthors = Ekblad E, Sundler F | title = Distribution of pancreatic polypeptide and peptide YY | journal = Peptides | volume = 23 | issue = 2 | pages = 251–261 | date = February 2002 | pmid = 11825640 | doi = 10.1016/S0196-9781(01)00601-5 | s2cid = 23262522 }} * {{cite journal | vauthors = Sandström O, El-Salhy M | title = Ontogeny and the effect of aging on pancreatic polypeptide and peptide YY | journal = Peptides | volume = 23 | issue = 2 | pages = 263–267 | date = February 2002 | pmid = 11825641 | doi = 10.1016/S0196-9781(01)00603-9 | s2cid = 6661540 }} * {{cite journal | vauthors = Yang H | title = Central and peripheral regulation of gastric acid secretion by peptide YY | journal = Peptides | volume = 23 | issue = 2 | pages = 349–358 | date = February 2002 | pmid = 11825649 | doi = 10.1016/S0196-9781(01)00611-8 | s2cid = 44727734 | url = https://zenodo.org/record/1259953 }} * {{cite journal | vauthors = Naruse S, Kitagawa M, Ishiguro H, Hayakawa T | title = Feedback regulation of pancreatic secretion by peptide YY | journal = Peptides | volume = 23 | issue = 2 | pages = 359–365 | date = February 2002 | pmid = 11825650 | doi = 10.1016/S0196-9781(01)00612-X | s2cid = 12150464 }} * {{cite journal | vauthors = Aponte GW | title = PYY-mediated fatty acid induced intestinal differentiation | journal = Peptides | volume = 23 | issue = 2 | pages = 367–376 | date = February 2002 | pmid = 11825651 | doi = 10.1016/S0196-9781(01)00613-1 | s2cid = 37633831 }} * {{cite journal | vauthors = Hagan MM | title = Peptide YY: a key mediator of orexigenic behavior | journal = Peptides | volume = 23 | issue = 2 | pages = 377–382 | date = February 2002 | pmid = 11825652 | doi = 10.1016/S0196-9781(01)00614-3 | s2cid = 11208314 }} * {{cite journal | vauthors = Mannon PJ | title = Peptide YY as a growth factor for intestinal epithelium | journal = Peptides | volume = 23 | issue = 2 | pages = 383–388 | date = February 2002 | pmid = 11825653 | doi = 10.1016/S0196-9781(01)00615-5 | s2cid = 33363834 | url = https://zenodo.org/record/1259955 }} * {{cite journal | vauthors = Tseng WW, Liu CD | title = Peptide YY and cancer: current findings and potential clinical applications | journal = Peptides | volume = 23 | issue = 2 | pages = 389–395 | date = February 2002 | pmid = 11825654 | doi = 10.1016/S0196-9781(01)00616-7 | s2cid = 38479590 }} * {{cite journal | vauthors = El-Salhy M, Suhr O, Danielsson A | title = Peptide YY in gastrointestinal disorders | journal = Peptides | volume = 23 | issue = 2 | pages = 397–402 | date = February 2002 | pmid = 11825655 | doi = 10.1016/S0196-9781(01)00617-9 | s2cid = 45335940 }} * {{cite journal | vauthors = Imamura M | title = Effects of surgical manipulation of the intestine on peptide YY and its physiology | journal = Peptides | volume = 23 | issue = 2 | pages = 403–407 | date = February 2002 | pmid = 11825656 | doi = 10.1016/S0196-9781(01)00618-0 | s2cid = 6023629 }} * {{cite journal | vauthors = Beglinger C, Degen L | title = Gastrointestinal satiety signals in humans--physiologic roles for GLP-1 and PYY? | journal = Physiology & Behavior | volume = 89 | issue = 4 | pages = 460–464 | date = November 2006 | pmid = 16828127 | doi = 10.1016/j.physbeh.2006.05.048 | s2cid = 32598231 }} * {{cite journal | vauthors = Eberlein GA, Eysselein VE, Schaeffer M, Layer P, Grandt D, Goebell H, Niebel W, Davis M, Lee TD, Shively JE | display-authors = 6 | title = A new molecular form of PYY: structural characterization of human PYY(3-36) and PYY(1-36) | journal = Peptides | volume = 10 | issue = 4 | pages = 797–803 | year = 1989 | pmid = 2587421 | doi = 10.1016/0196-9781(89)90116-2 | s2cid = 3857458 }} * {{cite journal | vauthors = Facer P, Bishop AE, Cole GA, Aitchison M, Kendall CH, van Aswegen G, Penketh RJ, Rodek CH, McKeever P, Polak JM | display-authors = 6 | title = Developmental profile of chromogranin, hormonal peptides, and 5-hydroxytryptamine in gastrointestinal endocrine cells | journal = Gastroenterology | volume = 97 | issue = 1 | pages = 48–57 | date = July 1989 | pmid = 2721879 | doi = 10.1016/0016-5085(89)91414-5 | doi-access = free }} * {{cite journal | vauthors = Tatemoto K, Nakano I, Makk G, Angwin P, Mann M, Schilling J, Go VL | title = Isolation and primary structure of human peptide YY | journal = Biochemical and Biophysical Research Communications | volume = 157 | issue = 2 | pages = 713–717 | date = December 1988 | pmid = 3202875 | doi = 10.1016/S0006-291X(88)80308-5 | bibcode = 1988BBRC..157..713T | doi-access = free }} * {{cite journal | vauthors = Lukinius AI, Ericsson JL, Lundqvist MK, Wilander EM | title = Ultrastructural localization of serotonin and polypeptide YY (PYY) in endocrine cells of the human rectum | journal = The Journal of Histochemistry and Cytochemistry | volume = 34 | issue = 6 | pages = 719–726 | date = June 1986 | pmid = 3517149 | doi = 10.1177/34.6.3517149 | doi-access = free }} * {{cite journal | vauthors = Adrian TE, Ferri GL, Bacarese-Hamilton AJ, Fuessl HS, Polak JM, Bloom SR | title = Human distribution and release of a putative new gut hormone, peptide YY | journal = Gastroenterology | volume = 89 | issue = 5 | pages = 1070–1077 | date = November 1985 | pmid = 3840109 | doi = 10.1016/0016-5085(85)90211-2 | doi-access = free }} * {{cite journal | vauthors = Lundell I, Blomqvist AG, Berglund MM, Schober DA, Johnson D, Statnick MA, Gadski RA, Gehlert DR, Larhammar D | display-authors = 6 | title = Cloning of a human receptor of the NPY receptor family with high affinity for pancreatic polypeptide and peptide YY | journal = The Journal of Biological Chemistry | volume = 270 | issue = 49 | pages = 29123–29128 | date = December 1995 | pmid = 7493937 | doi = 10.1074/jbc.270.49.29123 | doi-access = free }} * {{cite journal | vauthors = Bard JA, Walker MW, Branchek TA, Weinshank RL | title = Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY | journal = The Journal of Biological Chemistry | volume = 270 | issue = 45 | pages = 26762–26765 | date = November 1995 | pmid = 7592911 | doi = 10.1074/jbc.270.45.26762 | doi-access = free }} * {{cite journal | vauthors = Hort Y, Baker E, Sutherland GR, Shine J, Herzog H | title = Gene duplication of the human peptide YY gene (PYY) generated the pancreatic polypeptide gene (PPY) on chromosome 17q21.1 | journal = Genomics | volume = 26 | issue = 1 | pages = 77–83 | date = March 1995 | pmid = 7782089 | doi = 10.1016/0888-7543(95)80085-Z | author-link3 = Grant Robert Sutherland }} * {{cite journal | vauthors = Kohri K, Nata K, Yonekura H, Nagai A, Konno K, Okamoto H | title = Cloning and structural determination of human peptide YY cDNA and gene | journal = Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression | volume = 1173 | issue = 3 | pages = 345–349 | date = June 1993 | pmid = 8318545 | doi = 10.1016/0167-4781(93)90136-2 }} {{refend}}

== External links == * {{MeshName|Peptide+YY}}

{{PDB Gallery|geneid=5697}} {{Gastrointestinal hormones}}

{{DEFAULTSORT:Peptide Yy}} Category:Peptide hormones Category:Nutrition Category:Obesity