Figure 6. PDE Inhibition Protects against Diet-Induced Obesity and Glucose Intolerance.

(A) Rolipram increases the phosphorylation of ACC and AMPK in WAT. After 14 weeks of rolipram (2 mg/kg/day) treatment, epididymal fat was isolated from mice and analyzed for AMPK and ACC phosphorylation. Quantification of phoshorylation intensity is shown on the right (n = 4).

(B) Rolipram protects against diet-induced obesity. Mice fed HFD were treated with either saline (vehicle) or rolipram (2 mg/kg/day) and the weight gain during treatment is shown (n = 10 per group).

(C) The fat mass index (fat mass/total body weight) of mice from (B) was measured by NMR spectrometry (n = 10).

(D) HFD intake for vehicle- and rolipram-treated mice measured during weeks 1–4 of the treatment (n = 5).

(E) Twenty-four hour oxygen consumption (VO₂) of mice treated with either rolipram or vehicle for 12–14 weeks. A 24 hr average of VO₂ is shown on the right (n = 6).

(F) Rolipram does not affect locomotor activity. Twenty-four hour locomotor activity level was measured by beam-breaks (n = 5).

(G) Rolipram increases thermogenesis. The rectal temperatures of mice treated with either rolipram or vehicle in the fed or fasting (overnight) state (n = 7–10) are shown.

(H) Rolipram increases the expression of genes important for thermogenesis in WAT. The transcriptional levels of PGC-1α, the uncoupling proteins, and eNOS in WAT after 14 weeks of rolipram treatment were determined by real-time PCR (n = 5).

(I) ROS levels in WAT were measured by relative DCF fluorescence in WAT extract and shown as a percentage of that in control mice (n = 5).

(J) Glucose tolerance test (left) and the area under the curve (AUC) (right) are shown for HFD-fed mice treated with either rolipram or vehicle for 12–14 weeks (n = 7–10).

(K) The serum levels of GLP-1 were measured in mice treated for 7 weeks with resveratrol or rolipram (n = 4–8).

Results are expressed as the mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001 between treatment groups.