Glucagon-like peptide 2 (GLP-2) is a gut hormone involved in a variety of central and peripheral functions. GLP-2 central administration inhibits food intake, while no effect has been found by peripheral administration in long-term studies. We investigated the effects of i.p. administration of the GLP-2 stable analogue, [Gly²] -GLP-2, on food consumption in lean and diet-induced obese (DIO) mice. Mice, fasted for 16 h prior to study days, were injected i.p. with drugs or an equivalent volume of PBS. Food intake (Kcal/g of chow) was measured at intervals 1, 2, 4, 8 and 24 h post-injection.

In both lean and DIO mice, [Gly²]-GLP-2 (0.30 - 0.90 mg/g) dose-dependently and significantly inhibited food intake in comparison with PBS-treated mice. For both lean and DIO mice, the reduction in food intake occurred in the first hour post injection; it was sustained until 4 h post injection in lean mice and until 2 h post injection in DIO mice. No reduction was observed after 4 h in both animal models. The [Gly²] -GLP-2 effects on food intake were blocked by GLP-2 (3-33) (0.90 mg/g), GLP-2 receptor antagonist in both lean and DIO mice. The [Gly²]-GLP-2 anorectic action was significantly reduced in DIO compared with lean mice. This study shows for the first time that [Gly²]-GLP-2 is able to reduce food intake both lean and DIO mice, although with a different efficacy. On the basis of our results, GLP-2 might be suggested to play a role as anorectic hormone in the short-term.