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Peptide YY

PDB rendering based on 1qbf.
Available structures
1qbf, 1ru5, 1ruu, 2dez, 2df0
Identifiers
Symbols PYY; PYY1
External IDs OMIM: 600781 MGI: 99924 HomoloGene: 3066 GeneCards: PYY Gene
Orthologs
Species Human Mouse
Entrez 5697 217212
Ensembl ENSG00000131096 ENSMUSG00000017311
UniProt P10082 Q3V334
RefSeq (mRNA) NM_004160 NM_145435
RefSeq (protein) NP_004151 NP_663410
Location (UCSC) Chr 17:
39.39 - 39.44 Mb		 Chr 11:
101.92 - 101.92 Mb
PubMed search [1] [2]

Peptide YY is a short (36 amino acid) protein released by cells in the ileum and colon in response to feeding. In humans it appears to reduce appetite.

It is also known as PYY, Peptide Tyrosine Tyrosine, or Pancreatic Peptide YY3-36.[1]

Contents

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.[2] There are two major forms of Peptide YY: PYY1-36 and PYY3-36 which have PP fold structural motif. However, the most common form of circulating PYY immunoreactivity is PYY3-36 which binds to Y2 receptor (Y2R) of Y family receptors.[3] Peptide YY3-36 (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. There is also a small amount of PYY about 1-10 percent in esophagus, stomach, duodenum and jejunum.[4] PYY concentration in the circulation increases postprandially (after food ingestion) and decreases by fasting.[3] 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.[5]

Function

PYY exerts its action through NPY receptors, inhibits gastric motility and increases water and electrolyte absorption in the colon.[6] 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 meal. Research has also indicated that PYY may be useful in removing aluminium (aluminum) accumulated in the brain.

Animal studies

Several studies have shown that acute peripheral administration of PYY3-36 inhibits feeding of rodents and primates. Some more studies on Y2R-knockout mice have been done, and the result has revealed that there is no anorectic effect on Y2R-knock out mice. This findings indicate that PYY3-36 has anorectic ( losing appetite) effect which is suggested to be mediated by Y2R. Some studies have been done to investigate the effect of PYY on mice. Pyy-knock out 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 with high-fat diet, compare to control mice. Thus PYY also plays very important role in energy homeostasis by balancing the food intake.[3]

Relevance to obesity

Leptin also reduces appetite in response to feeding, but obese people develop a resistance to leptin. It has also been known that obese people secrete less PYY than non-obese people. On the other hand, attempts to use PYY directly as a weight-loss drug have met with some success. Researchers noted that caloric intake during a buffet lunch offered two hours after the infusion of PYY was decreased by 30 percent in obese subjects (P<0.001) and 31 percent in lean subjects (P<0.001).[7]

While some studies have shown that obese persons have lower circulating level of PYY postprandially, other studies have reported that obese people have normal sensitivity to anoretic effect of PYY3-36. Also, obese and non-obese people show no differences in PYY concentration. Thus, reduction in PYY secretion may not be one of the causes of obesity. However, the anoretic effect of PYY could possibly be a future obesity drug.[3]

Research done in 2006 showed that consumption of protein boosts PYY levels, therefore some benefit was observed in experimental subjects in terms of reducing hunger and promoting weight loss. This would help explain the weight-loss experienced with high-protein diets.

Soy isoflavones show structural and functional similarities to estradiol. Available data indicate that estradiol and estradiol-like components may interact with gut "satiety hormones" such as peptide YY (PYY) and ghrelin, and thus influence body weight. In a randomized, double-blind, placebo-controlled, cross-over trial with 34 healthy postmenopausal women (59 ± 6 years, BMI: 24.7 ± 2.8 kg/m2), isoflavone-enriched cereal bars (50 mg isoflavones/day; genistein to daidzein ratio 2:1) or non-isoflavone-enriched control bars were consumed for 8 weeks (wash-out period: 8-weeks). Seventeen of the subjects were classified as equol producers. Plasma concentrations of ghrelin and PYY, as well as energy intake and body weight were measured at baseline and after four and eight weeks of each intervention arm.[8]

References

  1. ^ "Entrez Gene: PYY peptide YY". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5697.  
  2. ^ DeGroot, Leslie Jacob (1989). J. E. McGuigan. ed. Endocrinology. Philadelphia: Saunders. p. 2754. ISBN 0-7216-2888-5.  
  3. ^ a b c d 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.  
  4. ^ Taylor IL (March 1985). "Distribution and release of peptide YY in dog measured by specific radioimmunoassay". Gastroenterology 88 (3): 731–7. PMID 3838162.  
  5. ^ 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.  
  6. ^ 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.  
  7. ^ 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.  
  8. ^ Weickert MO, Reimann M, Otto B, Hall WL, Vafeiadou K, Hallund J, Ferrari M, Talbot D, Branca F, Bügel S, Williams CM, Zunft HJ, Koebnick C (2006). "Soy isoflavones increase preprandial peptide YY (PYY), but have no effect on ghrelin and body weight in healthy postmenopausal women". J Negat Results Biomed 5: 11. doi:10.1186/1477-5751-5-11. PMID 16907966.  

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, 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, et al. (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, et al. (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. PMID 3517149.  
  • Adrian TE, Ferri GL, Bacarese-Hamilton AJ, et al. (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, et al. (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, et al. (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, et al. (1993). "Cloning and structural determination of human peptide YY cDNA and gene.". Biochim. Biophys. Acta 1173 (3): 345–9. PMID 8318545.  

See also

External links

Hormones: gastrointestinal hormones







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