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Role of peptide YY in 5-fluorouracil-induced reduction of dietary intake
- Source :
- Clinical and Experimental Pharmacology and Physiology. 43:753-759
- Publication Year :
- 2016
- Publisher :
- Wiley, 2016.
-
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.
- Subjects :
- Male
0301 basic medicine
Antimetabolites, Antineoplastic
medicine.medical_specialty
Physiology
medicine.drug_class
media_common.quotation_subject
030209 endocrinology & metabolism
Anorexia
Cachexia
Eating
Mice
Random Allocation
03 medical and health sciences
0302 clinical medicine
Glucagon-Like Peptide 1
Physiology (medical)
Internal medicine
medicine
Animals
Peptide YY
media_common
Pharmacology
business.industry
digestive, oral, and skin physiology
Appetite
Proglucagon
medicine.disease
Neuropeptide Y receptor
Receptor antagonist
Glucagon-like peptide-1
Mice, Inbred C57BL
030104 developmental biology
Endocrinology
Fluorouracil
medicine.symptom
business
hormones, hormone substitutes, and hormone antagonists
Subjects
Details
- ISSN :
- 03051870
- Volume :
- 43
- Database :
- OpenAIRE
- Journal :
- Clinical and Experimental Pharmacology and Physiology
- Accession number :
- edsair.doi.dedup.....8f388ffb9bbecf7a868e096a6ddea0bf