Purpose:To evaluate the effects of body fat reduction on insulin sensitivity, it was measured the glucose disappearance rate, glucose infusion rate, and hepatic glucose production rate after paraxanthine (1,7-dimethylxanthine, metabolite of caffeine) treatment in monosodium -L-glutamate (MSG)-obese rats.
Materials and Methods:Obesity was induced by neonatal (2, 4, 6, 8, 10 days) injection of MSG(4 g/kg, subcutaneously) for 15 weeks. MSG-obese rats showed severe fat deposition in subcutaneous and intraabdominal cavity, shortened body length, normoglycemia, hyperinsulinemia, and high FFA level. Insulin sensitivity was assessed with hyperinsulinemic euglycemic clamp technique under anesthesia with pentothal sodium. Plasma insulin concentration was clamped at 100 μU/ml by continuous insulin infusion (1.5 mU/kg/min). At steady state, the glucose disappearance rate and glucose infusion rate were decreased and the hepatic glucose production rate was increased in the MSG-obese rats compared to the normal rats.
Results
:At 15 weeks of age, paraxanthine (15 mg/kg) was administered with ephedrine (60 mg/kg) via per oral for 15 consecutive days. Body fat mass of the paraxanthine treated rats was decreased about 29.6% in the MSG-obese and 6.3% in the normal rats compared with the control rats during 15 days. In the paraxanthine treated MSG-obese rats, the fasting insulin level was significantly (p<0.05) decreased and the glucose infusion rate was significantly (p<0.05) increased compared to that of the MSG-control rats, however the glucose disappearance rate showed increasing tendency and the hepatic glucose production rate showed decreasing tendency compared to that of the MSG-control rats.
Conclusion
:These results suggest that paraxanthine exerts an anti-obesity effect and improve insulin sensitivity in rats with MSG-induced obesity.