Acute activation of adipocyte Gs signaling improves glucose homeostasis in obese mice. (A) Body weight gain of adipo-GsD and control mice maintained on a high-fat diet (HFD). (B–D) CNO challenge tests. HFD mice that had been fasted overnight were injected with CNO (10 mg/kg, i.p.), and blood glucose levels (B), plasma insulin levels (C), and plasma FFA levels (D) were measured at the indicated time points. (E) Intraperitoneal glucose tolerance test (IGTT, 1 g glucose/kg, i.p.). (E) Insulin tolerance test (ITT, 1 U/kg, i.p.). (F) Glucose-stimulated insulin secretion (GSIS, 1 g glucose/kg, i.p.). Data represent mean ± s.e.m. (mouse numbers are indicated in each panel). The experiments shown in (B–G) were obtained with male mice (littermates) that had been maintained on the HFD for at least 8 weeks. *P < 0.05, **P < 0.01, and ***P < 0.001 vs. control. Statistical significance was determined by two-way ANOVA followed by Bonferroni's post-hoc test.