Peptide YY

Source: Wikipedia, the free encyclopedia.
Not to be confused with Neuropeptide Y.
Not to be confused with Pancreatic polypeptide.
"PYY" redirects here. For the IATA code PYY, see Pai Airport.
PYY
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
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

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

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

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

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.[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. ^ 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. PMID 18987269
    .
  7. PMID 19073185
    .
  8. ISBN 978-0-7216-2888-2
    .
  9. ^
    S2CID 1120344
    .
  10. PMID 6953409
    .
  11. PMID 3838162
    .
  12. S2CID 16104580
    .
  13. PMID 18406449
    .
  14. PMID 24251972
    .
  15. PMID 16819834
    .
  16. PMID 24900634
    .
  17. S2CID 7082920
    .
  18. PMID 8607584
    .
  19. ^ "UF researchers use oral peptide spray to stimulate weight loss in animals". Dec 19, 2013.
  20. PMID 22028819
    .
  21. S2CID 40358403
    .
  22. S2CID 11764433
    .
  23. PMID 16950139
    .
  24. PMID 24057293
    .

Further reading

External links
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