Fig. 3: GLP1RA activation across targeted GLP1R-expressing brain regions.
From: A brain reward circuit inhibited by next-generation weight-loss drugs in mice
a–d, Glp1r-Cre;tdTomato mice mark GLP1R-positive neurons; FOS activation after treatment with vehicle, danuglipron, orforglipron or liraglutide in WT and Glp1rS33W mice in the DMH (a), NTS (b), AP (c) or CeA (d). Scale bar, 200 µm. e–h, Quantification of FOS in the DMH (e), NTS (f), AP (g) and CeA (h). Vehicle: DMH and CeA, n = 4 (WT), n = 3 (S33W); NTS and AP, n = 3 per genotype. Orforglipron and liraglutide: n = 4 per genotype in all regions. Danuglipron: NTS and AP, n = 4 (WT), n = 3 (S33W); DMH and CeA, n = 4 per genotype. i, Heat map of FOS activity in brain regions of interest across drug and vehicle conditions, normalized to WT vehicle. j, Ratio of NTS to AP FOS activation in Glp1rS33W mice after treatment with danuglipron (n = 3), orforglipron (n = 4) or liraglutide (n = 4). k,l, Neuronal FOS activation in the NTS and AP after administration of danuglipron (k) or orforglipron (l) to WT and Glp1rS33W mice by oral gavage. m,n, Quantification of FOS expression in the NTS (m) or AP (n) after IP or oral delivery of danuglipron or orforglipron in Glp1rS33W mice. Sample sizes: danuglipron oral, n = 6 (NTS and AP); danuglipron IP, n = 3 (NTS and AP); all other groups, n = 4. Data are mean ± s.e.m. Statistical tests: two-way ANOVA with Bonferroni correction (e–h,m,n); Kruskal–Wallis test (j). *P < 0.05; **P < 0.01; ***P < 0.001.
