title: Role of peptide YY in 5-fluorouracil-induced reduction of dietary intake.
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 this study examined the roles of these gut hormones in 5-FU-induced reduction of dietary intake. Mice were given 5-FU (50 mg/kg, intraperitoneal [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 i.p. route 30 minutes 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.
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Sakai
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kai
authors.affiliation: Department of Pharmacology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Takase
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Kimura
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Shoko
authors.initials: S
authors.lastname: Tabata
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Miyabi
authors.initials: M
authors.lastname: Yaegashi
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.affiliation: Division of Pharmacy Professional Development and Research, Department of Analytical Pathophysiology, Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yomoto
authors.affiliation: Department of Pharmacology, Hoshi University, Shinagawa-ku, Tokyo, Japan.|Life Science Tokyo Advanced Research Center (L-StaR), Hoshi University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Narita
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D004435:Eating / Q000187:drug effects* / Q000502:physiology*; D005472:Fluorouracil / Q000633:toxicity*; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019894:Peptide YY / Q000502:physiology*; D011897:Random Allocation
chemical_list: D000964:Antimetabolites, Antineoplastic; D019894:Peptide YY; D052216:Glucagon-Like Peptide 1; D005472:Fluorouracil
keywords: 5-fluorouracil; anorexia; chemotherapy; colon; glucagon-like peptide (GLP)-1; peptide YY