Fig. 3: PNS-specific loss of Gipr has no effect on weight loss in DIO mice induced by GLP-1R agonism–GIPR antagonism co-therapy. | Nature Metabolism

Fig. 3: PNS-specific loss of Gipr has no effect on weight loss in DIO mice induced by GLP-1R agonism–GIPR antagonism co-therapy.

From: GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice

Fig. 3: PNS-specific loss of Gipr has no effect on weight loss in DIO mice induced by GLP-1R agonism–GIPR antagonism co-therapy.The alternative text for this image may have been generated using AI.

a, Acute food intake of 49-week-old male C57BL/6J DIO Per-Cre+Giprwt/wt (WT) or Per-Cre+Giprflx/flx (KO) mice treated s.c. with a single dose of either vehicle (Vhcl) or acyl-GIP (100 nmol kg−1). b–d, Body weight development (b), placebo-corrected weight loss after 25 days treatment (c) and food intake (d) of 47-week-old male C57BL/6J WT and Per-Gipr KO mice treated daily with either vehicle, acyl-GLP-1 (10 nmol kg−1) or the combination of acyl-GLP-1 (10 nmol kg−1) and a GIPR antagonist (ant.) (1,500 nmol kg−1) (n = 8 each group). e,f, Body composition (fat mass (e) and lean mass (f), n = 8 each group) of 47-week-old male C57BL/6J DIO WT and Per-Gipr KO mice after 25 days of treatment. g–i, i.p. glucose tolerance (g and h) with corresponding area under curve (AUC) (i) in 47-week-old male C57BL/6J DIO WT (g and i) and Per-Gipr KO mice (h and i) after 25 days of treatment with either vehicle (n = 8 WT and n = 8 KO), acyl-GLP-1 (n = 7 WT and n = 8 KO) or the co-therapy of acyl-GLP-1 and the GIPR antagonist (n = 8 WT and n = 8 KO). j, Fasting plasma levels of blood glucose in 47-week-old male DIO WT and Per-Gipr KO mice treated either with vehicle, acyl-GLP-1 or the co-therapy of acyl-GLP-1 and the GIPR antagonist (n = 8 each group). k,l, Fasting plasma levels of insulin (k) and corresponding HOMA-IR (l) in 47-week-old male DIO WT and Per-Gipr KO mice treated either with vehicle (n = 8 WT and n = 8 KO), acyl-GLP-1 (n = 7 WT and n = 8 KO) or the co-therapy of acyl-GLP-1 and the GIPR antagonist (n = 8 WT and n = 8 KO). m, Ad libitum plasma levels of triglycerides in 47-week-old male DIO WT and Per-Gipr KO mice (n = 8 mice each group). Data in a, b, g and h were analysed by a two-way ANOVA with Bonferroni’s post hoc test for comparison of individual timepoints. Data in c–f and i–m were analysed using a one-way ANOVA. Cumulative food intake (d) was assessed per cage in n = 8 double- or single-housed mice each group. Data represent mean ± s.e.m. *P < 0.05, **P < 0.01 and ***P < 0.001. The asterisk colours in a correspond to the comparison of vehicle versus acyl-GIP in WT (black) and Per-GIPR KO (red) mice. The asterisk colours in b correspond to the comparison of acyl-GLP-1 versus the co-therapy in WT (blue) and Per-GIPR KO (red) mice. Individual P values are shown in the Source data, unless P < 0.0001.

Source data.

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