Fig. 4: Effects of inhibition of GLP-1R, GIPR or PPARδ in mice.
From: GLP-1R–GIPR–PPARα/γ/δ quintuple agonism corrects obesity and diabetes in mice
a,b, DIO wild-type (WT) and Vglut2/Glp1r-knockout (KO) mice were treated once daily with subcutaneous injections of vehicle or 10 nmol kg−1 GLP-1–GIP or GLP-1–GIP–Lani for 14 days. n = 8–9 mice per group. a, Body weight. b, Cumulative food intake. c, Change in body weight of DIO wild-type and Gipr-knockout mice treated once daily with subcutaneous injections of vehicle or 10 nmol kg−1 GLP-1–GIP or GLP-1–GIP–Lani for 14 days. n = 7–8 mice per group. d–f, DIO mice were treated once daily with subcutaneous injections of vehicle or 10 nmol kg−1 acyl-GIP, GLP-1–Lani, GLP-1–GIP–Lani or GLP-1–Lani plus acyl-GIP for 14 days. n = 7–8 mice per group. d, Body weight. e, Cumulative food intake. f, Glucose tolerance test at day 14. g,h, DIO mice were treated once daily for 14 days with intraperitoneal injections of the PPARδ agonist GW501516 (11 μmol kg−1), subcutaneous injections of GLP-1–GIP–Lani (10 nmol kg−1) or vehicle, or pretreated intraperitoneally with the PPARδ antagonist GSK3787 (25.5 μmol kg−1) 4 h before administration of GW501516 or GLP-1–GIP–Lani. n = 6–8 mice per group. g, Ad libitum blood glucose at day 11. h, Body weight. i–m, DIO wild-type and DIR-knockout mice were treated once daily with subcutaneous injections of vehicle or 10 nmol kg−1 GLP-1–GIP–Lani for 7 days. n = 7–8 mice per group. i, Body weight. j, Cumulative food intake. k, Glucose tolerance test at day 7. l, Fasting blood glucose. m, Fasting plasma insulin. Data were analysed using one-way ANOVA with Bonferroni post hoc multiple-comparison test (g,m), two-way repeated-measures ANOVA (a–f,h–k) or Kruskal–Wallis test with uncorrected Dunns’s test (l). Cumulative food intake (e,j) was assessed per cage in single- or double-house mice. Data are mean ± s.e.m. Exact P values, n values and detailed statistics are provided in Supplementary Tables 1 and 3 and Source Data.
