A–C, Cnr2 knock-out reduces obesity-induced insulin resistance. WT and Cnr2 −/− mice were fed a ND or a HFD for 15 weeks A, Fasting glycemia, insulinemia, HOMA-IR; B, Blood glucose level during insulin tolerance tests in HFD-fed mice (p<0.05 by two way ANOVA). C, Hyperinsulinemic-euglycemic clamp in HFD-fed mice, as assessed by glucose turnover rate, whole body glycolysis and glycogen synthesis, following insulin stimulation. D, CB2 receptor activation increases insulin resistance. Blood glucose level during insulin tolerance tests in WT mice fed a HFD for 6 weeks and treated daily with an i.p injection of JWH-133 (3 mg/kg) or vehicle during the last 15 days of HFD (p<0.05 by two way ANOVA). * p<0.05 for HFD-fed Cnr2 −/− vs HFD-fed WT mice. # p<0.05 in HFD-fed WT vs ND-fed WT mice.