Effect of rimonabant on improvement of glucose and lipid metabolism and CB_1 receptor expression in peripheral tissues in KKAy mice

Objective To investigate the relationship between the improvement of glucose and lipid disorders in KKAy mice by rimonabant and the expression of CB1 receptor(CB1R) in peripheral tissues.Methods Ten-week-old C57BL/6J and KKAy mice were randomly divided into two groups respectively: the vehicle control group and rimonabant(10 mg/kg) treatment group(n=8).The mice were treated for 26 days.Changes in body mass were monitored every day and fasting blood glucose was tested on the 20th day of treatment.At the end of the experiment,serum triglyceride(TG),total cholesterol(TC),insulin,leptin and adiponectin concentrations were determined.Liver and total fat parameters were weighed.The expression of CB1R in the liver and epididymal fat were determined by Western blot.Results(1) KKAy mice displayed characteristics of T2DM: with dysfunctions in blood glucose and lipids metabolism.Rimonabant could specifically ameliorate some dysfunctions of KKAy mice,as evidenced by the decreasing glucose,serum TC and insulin level,increasing serum adiponectin,and reducing body mass,liver and adipose weight index,but it had no these effect on C57 mice.(2) The expression of CB1R in the liver of KKAy mice significantly lowered,but remarkably higher than that of C57 mice in epididymal fat.The expression of CB1R in the epididymal fat of KKAy mice was six times more than that in the liver.(3) Rimonabant could significantly reduce CB1R expression in these tissues of KKAy mice.However,for the normal C57 mice,the effect on CB1R expression was slight.Conclusion Rimonabant could effectively ameliorate the metabolic disorders of glucose and lipid in KKAy mice,which is correlated with the down-regulated expression of CB1 receptor in the liver and especially in the epididymal fat of KKAy mice.