Insulin Resistance of Skeletal Muscle was Recovered by Leptin Injection in vivo, but not in vitro, in High-fat Diet Fed Rats

We examined the effect of leptin on the insulin resistance in skeletal muscles by measuring the glucose transport. Male Wistar rats were fed with chow or high-fat diets for 30 days. Three days before sacrifice, high-fat fed rats were subcutaneously injected with leptin (1 mg/kg body weight) for 3 days. The glucose transports in the epitrochlearis and soleus muscle were not different among the experimental groups under basal state, however these were decreased significantly in the high fat-diet rats under insulin-stimulation (p＜0.01). Leptin treatment recovered the decreased glucose transport in the epitrochlearis (p＜0.05) and soleus (p=0.08). Triglyceride concentration in the soleus muscle was increased significantly in the high fat-fed rats, compared to chow diet rats (p＜0.01), and it was decreased significantly by leptin treatment (p＜0.01). The glucose transport was measured under basal and $60{\mu}u/ml$ of insulin with or without 50 ng/ml of leptin. Leptin had no direct stimulatory effect on glucose transport under both basal and insulin-stimulated conditions in vitro. These results demonstrate that leptin injection to high fat diet fed rats recovered impaired insulin responsiveness of the skeletal muscles and muscle triglyceride concentration. However, there was no direct stimulatory effect of leptin on insulin sensitivity of the skeletal muscle in vitro.