TY - JOUR
T1 - The anorexic hormone Peptide YY3-36 is rapidly metabolized to inactive Peptide YY3-34 in vivo.
AU - Toräng, Signe
AU - Veedfald, Simon
AU - Rosenkilde, Mette Marie
AU - Hartmann, Bolette
AU - Holst, Jens Juul
N1 - M1 - Copyright (C) 2015 American Chemical Society (ACS). All Rights Reserved.
CAPLUS AN 2015:1289224(Journal; Online Computer File)
PY - 2015/7/20
Y1 - 2015/7/20
N2 - Peptide YY (PYY) is a 36 amino acid peptide hormone released from enteroendocrine cells. An N-terminally degraded metabolite, PYY3-36, 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 PYY3-36 into multicatheterized pigs (n = 7) (2 pmol/kg/min). Plasma samples were analyzed by regionspecific radioimmunoassays (RIA) and HPLC analysis. A metabolite, corresponding to PYY3-34 was formed after incubation in plasma and blood and during the infusion study. When taking the C-terminal degradation into account, the half-life (T½) of PYY in blood and plasma amounted to 3.4 ± 0.2 and 6.2 ± 0.2 h, respectively. After PYY3-36 infusion in pigs, the peptide was degraded with a T½ 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. PYY3-34 was unable to activate the Y2 receptor in a transfected cell line. In conclusion, PYY3-36 is extensively degraded to PYY3-34 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 PYY3-36, leading to underestimation of its physiological effects.
AB - Peptide YY (PYY) is a 36 amino acid peptide hormone released from enteroendocrine cells. An N-terminally degraded metabolite, PYY3-36, 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 PYY3-36 into multicatheterized pigs (n = 7) (2 pmol/kg/min). Plasma samples were analyzed by regionspecific radioimmunoassays (RIA) and HPLC analysis. A metabolite, corresponding to PYY3-34 was formed after incubation in plasma and blood and during the infusion study. When taking the C-terminal degradation into account, the half-life (T½) of PYY in blood and plasma amounted to 3.4 ± 0.2 and 6.2 ± 0.2 h, respectively. After PYY3-36 infusion in pigs, the peptide was degraded with a T½ 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. PYY3-34 was unable to activate the Y2 receptor in a transfected cell line. In conclusion, PYY3-36 is extensively degraded to PYY3-34 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 PYY3-36, leading to underestimation of its physiological effects.
U2 - 10.14814/phy2.12455
DO - 10.14814/phy2.12455
M3 - Journal article
SN - 2051-817X
VL - 3
SP - 1
EP - 8
JO - Physiological Reports
JF - Physiological Reports
IS - 7
M1 - e12455
ER -
