title: Food intake in lean and obese mice after peripheral administration of glucagon-like peptide 2.
abstract: We investigated the potential anorectic action of peripherally administered glucagon-like peptide 2 (GLP2) in lean and diet-induced obese (DIO) mice. Mice, fasted for 16 h, were injected i.p. with native GLP2 or [Gly2]GLP2, stable analog of GLP2, before or after GLP2 (3-33), a GLP2 receptor (GLP2R) antagonist, or exendin (9-39), a GLP1R antagonist. Food intake was measured at intervals 1, 2, 4, 8, and 24 h postinjection. In addition, we tested in lean mice the influence of [Gly2]GLP2 on gastric emptying and the effects of GLP1 alone or in combination with [Gly2]GLP2 on food intake. [Gly2]GLP2 dose dependently and significantly inhibited food intake in lean and DIO mice. The reduction of food intake occurred in the first hour postinjection and it was sustained until 4 h postinjection in lean mice while it was sustained until 2 h postinjection in DIO mice. GLP2 significantly inhibited food intake in both lean and DIO mice but only in the first hour postinjection. The efficiency of [Gly2]GLP2 or GLP2 in suppressing food intake was significantly weaker in DIO mice compared with lean animals. The [Gly2]GLP2 anorectic actions were blocked by the GLP2R antagonist GLP2 (3-33) or by the GLP1R antagonist exendin (9-39). The coadministration of [Gly2]GLP2 and GLP1 did not cause additive effects. [Gly2]GLP2 decreased the gastric emptying rate. Results suggest that GLP2 can reduce food intake in mice in the short term, likely acting at a peripheral level. DIO mice are less sensitive to the anorectic effect of the peptide.
authors.affiliation: Laboratorio di Fisiologia Generale, Dipartimento di Scienze e Tecnologie Molecolari e Biomolecolari (STEMBIO), Università di Palermo, Viale delle Scienze, 90128 Palermo, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Baldassano
authors.forename: Anna Lisa
authors.initials: AL
authors.lastname: Bellanca
authors.forename: Rosa
authors.initials: R
authors.lastname: Serio
authors.forename: Flavia
authors.initials: F
authors.lastname: Mulè
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005746:Gastric Emptying / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology; D053767:Glucagon-Like Peptide 2 / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor; D000067758:Glucagon-Like Peptide-2 Receptor; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000209:etiology / Q000503:physiopathology*; D010446:Peptide Fragments / Q000494:pharmacology*; D020239:Receptor Cross-Talk / Q000187:drug effects; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000502:physiology; D013997:Time Factors
chemical_list: D001067:Appetite Depressants; C000593834:Glp1r protein, mouse; D053767:Glucagon-Like Peptide 2; D000067757:Glucagon-Like Peptide-1 Receptor; D000067758:Glucagon-Like Peptide-2 Receptor; D010446:Peptide Fragments; D018027:Receptors, Glucagon; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1