Fat-induced ileal brake in the dog depends on peptide YY.
OBJECTIVE
Fat in the distal gut inhibits transit through the proximal small intestine as the ileal brake. Although the mediator of this response is not established, peptide YY (PYY) has been considered the most likely peptide candidate because inhibition of intestinal motility by fat in the distal gut correlated with the release of PYY but not other distal gut peptides such as enteroglucagon or neurotensin. Although intravenous administration of PYY inhibits intestinal transit, the role of this peptide remains to be confirmed because systemic PYY may not exert its effect by the same regulatory pathway as fat-induced ileal brake. The aim of this study was to definitively test the hypothesis that PYY mediates fat-induced ileal brake using the technique of peptide immunoneutralization.


METHODS
In a fistulated dog model, intestinal transit during perfusion of the distal gut with 60 mmol/L oleate (ileal brake) was examined after intravenous administration of 0.5 mg/kg of PYY antibody (anti-PYY), nonspecific immunoglobulin G (control), or 0.15 mol/L NaCl. Intestinal transit result (cumulative percent recovery of 99mTc) was normalized within each animal against the transit result of the 0.15 mol/L NaCl experiment.


RESULTS
Intestinal transit accelerated with PYY immunoneutralization, increasing cumulative percent recovery from 25.9 +/- 6.2 (control) to 81.2 +/- 6.3 (anti-PYY).


CONCLUSIONS
Fat-induced ileal brake depends on PYY.
Lin
H C
HC
Department of Medicine, Cedars-Sinai Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Zhao
X T
XT
Wang
L
L
Wong
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D004285:Dogs; D005772:Gastrointestinal Transit / Q000187:drug effects; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D007074:Immunoglobulin G / Q000494:pharmacology; D019301:Oleic Acid; D009829:Oleic Acids / Q000008:administration & dosage / Q000494:pharmacology*; D019894:Peptide YY; D010455:Peptides / Q000276:immunology / Q000502:physiology*; D010477:Perfusion
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D009829:Oleic Acids; D010455:Peptides; D019894:Peptide YY; D019301:Oleic Acid