Extended Data Fig. 4: Chemogenetic activation of PVNGLP-1R→DVC neurons via hM3Dq suppresses food intake.
From: State-dependent central synaptic regulation by GLP-1 is essential for energy homeostasis
a. Food intake consumption after i.p. saline injection (control) in GLP1R-ires-Cre mice expressing hM3Dq- or control-virus in PVNGLP-1R→DVC neurons during the dark cycle (related to Fig. 2e) (two-way ANOVA, Group effect: F(1, 14) = 2.492, p = 0.1368; Time effect: F(3, 42) = 89.98, p < 0.0001; interaction: F(3, 42) = 0.6374, p = 0.5952, control n = 9 mice, hM3Dq n = 7 mice). b. Food intake upon activation of PVNGLP-1R→DVC neurons in a fasted-refeeding paradigm during the light cycle (two-way ANOVA, main effect of Group: F(1, 14) = 10.83, p = 0.0054; main effect of Time: F(1.570, 21.98) = 60.54, p < 0.0001; interaction between Group and Time: F(3, 42) = 1.921, p = 0.1408; Sidak’s multiple comparisons test vs. control: 30 min p = 0.0056; 60 min p = 0.0188; 120 min p = 0.0296; 180 min p = 0.0346; control n = 9 mice, hM3Dq n = 7 mice). c. Food intake consumption upon activation of PVNGLP-1R→DVC neurons in the fed light cycle (two-way ANOVA, Group effect: F(1, 14) = 6.781, p = 0.0208; Time effect: F(1.903, 26.64) = 21, p < 0.0001; interaction: F(3, 42) = 3.899, p = 0.0152; Sidak’s multiple comparisons test vs. control: 30 min p = 0.063; 60 min p = 0.2495; 120 min p = 0.0623; 180 min p = 0.0256; control n = 9 mice, hM3Dq n = 7 mice). d. Glucose tolerance test with or without chemogenetic activation (two-way ANOVA, Group effect: F(1, 14) = 1.663, p = 0.2181; Time effect: F(2.740, 38.36) = 355.1, p < 0.0001; interaction: F(4, 56) = 1.342, p = 0.2659; control n = 9 mice, hM3Dq n = 7 mice). e. Representative traces of animal exploration in the open field with or without chemogenetic activation of PVNGLP-1R→DVC neurons. f. Time spent in the center of the open field (two-tailed t-test, t (16) = 1.617, p = 0.1282; control n = 9 mice, hM3Dq n = 7 mice). g. Total traveled distance in the open field (two-tailed t-test, t(16) = 1.283, p = 0.2205; control n = 9 mice, hM3Dq n = 7 mice). h. Quantification of light-dark box assay for anxiety-like behaviors: time spent in the dark zone (two-tailed t-test, t(16) = 0.1509, p = 0.8822; control n = 9 mice, hM3Dq n = 7 mice). i. Dark zone entries (two-tailed t-test, t(16) = 0.0516, p = 0.9596; control n = 9 mice, hM3Dq n = 7 mice). Data are presented as mean ± standard error of the mean (SEM). ∗p < 0.05; ∗∗p < 0.01.
