Fig. 4: GLP1R activation in the CeA inhibits hedonic food intake.
From: A brain reward circuit inhibited by next-generation weight-loss drugs in mice
a, Schematic of AAV-DIO-hGLP1R delivery to the BMH. b–k, Homeostatic SD (b–f) or hedonic HFD (g–k) intake after treatment with vehicle or danuglipron in Glp1r-Cre mice expressing AAV-DIO-mCherry in the BMH (BMH-mCherry, n = 6) (b,g) or expressing AAV-DIO-hGLP1R (BMH-hGLP1R, n = 10) in the BMH (c,h), DMH (n = 7) (d,i), NTS–AP (n = 6) (e,j) or CeA (n = 9) (f,k). l, Schematic of AAV-DIO-mGLP1R (left) and AAV-DIO-hGLP1R (right) delivery in the CeA of Glp1r-Cre;tdTomato mice. h prefix denotes human; m prefix denotes mouse. m,n, Representative CeA images from l after treatment with vehicle (m) or danuglipron (n) (red, tdTomato; green, FOS; colocalization, white arrowheads). Scale bar, 100 µm. o, Quantification of FOS+tdTomato+ cells from m,n (Veh n = 3, Dan n = 4 per virus). p, Schematic of AAV-DIO-GCaMP7s plus AAV-DIO-mGLP1R or AAV-DIO-hGLP1R administration with fibre implant in the CeA of Glp1r-Cre mice. q,r, Heat maps of z-scored calcium signals during one hour of fibre photometry after treatment with vehicle or danuglipron in mGLP1R (q) or hGLP1R (r) mice (n = 6 per condition). s, Quantification of area under the curve (AUC) from q,r. t, Significant calcium event counts from q,r. u, Schematic of AAV-DIO-eYFP or AAV-DIO-ChR2-eYFP delivery with a fibre-optic implant in the CeA of Glp1r-Cre mice. v,w, Stimulation frequency response of one-hour SD (v) or HFD (w) intake in eYFP or ChR2 mice (n = 5 per group). x, Schematic of AAV-Cre (conditional Glp1r knockout) or AAV-GFP (control) delivery in the CeA of Glp1rflox/flox mice. y, Four-hour SD or HFD intake after treatment with liraglutide in GFP- or Cre-expressing mice (AAV-GFP n = 11, AAV-Cre n = 12). Data are mean ± s.e.m. Statistical tests: two-way ANOVA with Bonferroni correction (b–k,t,v,w); two-way ANOVA with Tukey’s HSD correction (o); unpaired t-test (s); Welch’s t-test (y). *P < 0.05; **P < 0.01; ***P < 0.001.
