(a) Experimental setup to measure the metabolic effects of liraglutide (panels b-f). (b) Cumulative food intake in the different light/dark phases 3 days after liraglutide treatment, compared to baseline (Night phase: two-way ANOVA, genotype: F(1, 28)= 1.64, p = 0.210; treatment: F(1, 28)= 42.36, p < 0.0001 interaction: F(1, 28)= 13.69, p = 0.0009. Tukey’s post hoc test, control saline vs. control liraglutide, p <0.0001and iBot saline vs. iBot liraglutide, p = 0.240; sum: two-way ANOVA, genotype: F(1, 28)= 2.63, p = 0.116; treatment: F(1, 28)= 16.59, p = 0.0003 interaction: F(1, 28)= 10.69, p = 0.0029. Tukey’s post hoc test, control saline vs. control liraglutide, p <0.0001and iBot saline vs. iBot liraglutide, p = 0.945) (n = 8, 9, 8, 7 mice). (c) Body weight change after the experiment shown in (a) (two-way ANOVA, genotype: F(1, 31)= 8.98, p = 0.53; treatment: F(1, 31)= 32.85 , p < 0.0001; interaction: F(1, 31)= 1.01, p = 0.324. Tukey’s post hoc test, control saline vs. control liraglutide, p = 0.0001and iBot saline vs. iBot liraglutide, p = 0.0154; control liraglutide vs. iBot liraglutide, p = 0.042) (n = 10, 9, 8, 8 mice). (d) Fat mass change after the experiment shown in (a). Data were analyzed using an unpaired one-tailed t-test (fat mass, t(18) = 2.53, p = 0.0104; body weight change, p = 0.0495) (n = 10, 10 mice). (e, f) Fatty acid oxidation and area under the curve (AUC) in control (e) and iBot (f) animals 3 days after liraglutide injection, compared to saline (n = 8 mice per group). Two-way ANOVA with Tukey’s post hoc test (control saline vs. control liraglutide: 20.00, p = 0.0191; 21.00, p = 0.0311; 22.00, p = 0.0061; 2.00, p = 0.0408; 4.00, p = 0.0066) (n = 9, 8 mice). Red dotted lines indicate liraglutide or vehicle administration. AUC, paired two-tailed t-test t(5) = 3.62 p = 0.0152, n = 6 mice in (e) and t(5) = 2.39, p = 0.0624, n = 6 mice in (f). iBot saline vs. iBot liraglutide, # p < 0.05; † p < 0.05 control liraglutide vs. iBot liraglutide, * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001.