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Abstract Title:

Role of peptide YY in 5-fluorouracil-induced reduction of dietary intake.

Abstract Source:

Clin Exp Pharmacol Physiol. 2016 Apr 30. Epub 2016 Apr 30. PMID: 27130783

Abstract Author(s):

Hiroyasu Sakai, Yuki Kai, Kazuhide Takase, Ken Sato, Minami Kimura, Shoko Tabata, Miyabi Yaegashi, Fumiaki Sato, Tetsuro Yomoto, Minoru Narita

Article Affiliation:

Hiroyasu Sakai

Abstract:

5-fluorouracil (5-FU) is part of the standard care for cancer treatment but is associated with high incidences of appetite loss and reduced food intake, which may contribute to chemotherapy-induced cachexia (weakness and wasting of tissue). The role of gastrointestinal satiety hormones in chemotherapy-induced appetite loss has not been intensively investigated. Peptide YY (PYY) and glucagon-like peptide (GLP)-1 are important signals of gastrointestinal satiety, so we examined the roles of these gut hormones in 5-FU-induced reduction of dietary intake. Mice were given 5-FU (50 mg/kg, i.p.) every day for 4 consecutive days. Gene expression levels of proglucagon (Pro-Gcg), a precursor of GLP-1, and PYY in the colon were examined by real-time RT-PCR. Serum levels of GLP-1 and PYY were measured by enzyme-linked immunosorbent assay. Some mice were pretreated with the GLP-1 receptor antagonist exendin9-39 (1 mg/kg) or the neuropeptide Y type 2 (NPY2) receptor antagonist BIIE0246 (2 mg/kg) via the intraperitoneal route 30 min before 5-FU administration. Mice receiving 5-FU exhibited a significant reduction in food intake that was correlated with body weight loss. These mice also showed significantly enhanced expression levels of mRNAs encoding pro-GLP-1 and PYY in the transverse and distal colon as well as elevated serum concentrations of GLP-1 and PYY compared to vehicle-treated controls. The 5-FU-induced reduction in food intake was attenuated by BIIE0246 but not by exendin9-39. These data suggest that administration of a NPY2 receptor antagonist may be effective for attenuating the anorexia caused by 5-FU chemotherapy. This article is protected by copyright. All rights reserved.

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Sayer Ji
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