The anorexic hormone Peptide YY3–36 is rapidly metabolized to inactive Peptide YY3–34 in vivo. Issue 7 (21st July 2015)

• Record Type: Journal Article
• Authors: Toräng, Signe; Veedfald, Simon; Rosenkilde, Mette Marie; Hartmann, Bolette; Holst, Jens Juul
• Is Part Of: Physiological reports. Volume 3:Issue 7(2015:Jul.)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2015-07-21
• Subjects: Physiology -- Periodicals; 571
• DOI: 10.14814/phy2.12455
• Languages: English
• ISSNs: 2051-817X

Abstract

<abstract abstract-type="main" id="phy212455-abs-0001"> <title>Abstract</title> <p>Peptide YY (PYY) is a 36 amino acid peptide hormone released from enteroendocrine cells. An N‐terminally degraded metabolite, PYY<sub>3–36, </sub> has anorexigenic effects, which makes the PYY system a target for obesity treatment. However, little is known about the kinetics and degradation products of PYY. A related peptide, Neuropeptide Y (NPY), may be degraded from the C‐terminus. We therefore investigated PYY degradation after in vitro incubations in porcine plasma and blood and in vivo by infusing PYY<sub>3–36</sub> into multicatheterized pigs (<italic>n</italic> = 7) (2 pmol/kg/min). Plasma samples were analyzed by region‐specific radioimmunoassays (RIA) and HPLC analysis. A metabolite, corresponding to PYY<sub>3–34</sub> was formed after incubation in plasma and blood and during the infusion study. When taking the C‐terminal degradation into account, the half‐life (<italic>T</italic>½) of PYY in blood and plasma amounted to 3.4 ± 0.2 and 6.2 ± 0.2 h, respectively. After PYY<sub>3–36</sub> infusion in pigs, the peptide was degraded with a <italic>T</italic>½ of 3.6 ± 0.5 min. Significant extraction (20.5 ± 8.0%) compatible with glomerular filtration was observed across the kidneys and significant C‐terminal degradation (26.5 ± 4.8%) was observed across the liver. Net balances across the hind limb, splanchnic bed, and lungs were not significantly different from zero. PYY<sub>3–34</sub> was unable to activate the Y2 receptor in a transfected cell line. In conclusion, PYY<sub>3–36</sub> is extensively degraded to PYY<sub>3–34</sub> in the pig, a degradation that renders the peptide inactive on the Y2 receptor. Currently used assays are unlikely to be able to detect this degradation and therefore measure falsely elevated levels of PYY<sub>3–36</sub>, leading to underestimation of its physiological effects.</p> </abstract>