Figure 3.

Chronic activation of adipocyte G_s signaling significantly decreases body weight and improves glucose homeostasis in mice consuming a HFD. All studies shown in this figure were carried out with male adipo-GsD and control mice that had been maintained on a HFD for 8 weeks and had received daily injections of CNO (10 mg/kg, i.p.) during the last 4 weeks of HFD feeding. (A) Body weight gain of HFD adipo-GsD and control mice chronically treated with CNO. (B) Representative photographs of inguinal WAT (iWAT), epididymal WAT (eWAT), and brown adipose tissue (BAT) following chronic CNO treatment. (C) Tissue weight of iWAT, eWAT and BAT after chronic CNO treatment. (D) Blood glucose, (E) plasma insulin, (F) plasma FFA, (G) plasma leptin, and (H) plasma adiponectin levels before and after chronic CNO administration. (I) Intraperitoneal glucose tolerance test (IGTT, 1 glucose/kg, i.p.) carried out after chronic CNO treatment. (L) Liver weight and (M) liver triglyceride (TG) content of mice following chronic CNO administration. (N) Images of liver sections stained with Oil Red O after chronic CNO treatment. (M) H&E staining of adipose tissues after chronic CNO treatment. (N) Expression of beiging-related genes in iWAT following chronic CNO administration. (O) Cold tolerance test (4 °C) after chronic CNO treatment. All studies were performed with male littermates. Data represent mean ± s.e.m. (mouse numbers are indicated in each panel). *P < 0.05, **P < 0.01, and ***P < 0.001 vs. control. Significance was determined by two-way ANOVA followed by Bonferroni's post-hoc test (A, D-I, O) or by two-tailed Student's t test (C, J, K, and N).