Fig. 1: GLP-1R agonism and GIPR antagonism have similar effects on metabolism in HFD-fed Vgat-Gipr KO mice.
a–c, Body weight development (a), placebo-corrected weight (b) and cumulative food intake (c) of 33-week-old male C57BL/6J WT or Vgat-Gipr KO mice treated daily over 24 days with either vehicle (Vhcl), 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 mice each group). d–h, Body composition (fat mass (d) and lean mass (e)) and i.p. glucose tolerance (f and g) with corresponding area under curve (h) of 36-week-old male C57BL/6J WT and Vgat-Gipr KO mice (n = 8 each group) after 24 days of treatment. i, Fasting plasma levels of blood glucose (n = 8 each group) in 36-week-old male C57BL/6J WT or Vgat-Gipr KO mice. j,k, Fasting plasma levels of insulin (j) and corresponding HOMA-IR (k) in in 36-week-old male C57BL/6J WT and Vgat-Gipr KO mice treated either with vehicle (n = 8 WT and n = 8 KO), acyl-GLP-1 (n = 8 WT and n = 8 KO) or the co-therapy of acyl-GLP-1 and the GIPR antagonist (n = 7 WT and n = 7 KO). l,m, Ad libitum plasma levels of triglycerides (l) and cholesterol (m) in 36-week-old male C57BL/6J WT or Vgat-Gipr KO mice (n = 8 mice each group). Data in a, c, f and g were analysed by repeated measures two-way ANOVA with Bonferroni’s post hoc test for comparison of individual timepoints. Data in b, d, e, h and i–m were analysed using one-way ANOVA. Cumulative food intake (c) was assessed per cage in n = 8 double-housed mice. Data represent mean ± s.e.m.; *P < 0.05, **P < 0.01 and ***P < 0.001. The blue asterisks in a and c correspond to the comparison of acyl-GLP-1 versus the co-therapy in WT mice, while red asterisks correspond to acyl-GLP-1 versus the co-therapy in the Vgat-Gipr KO mice. Individual P values are shown in the Source data, unless P < 0.0001.
