OBJECTIVE: In order to provide theoretic evidence of exercise preventing insulin resistance, we studied the effects of high-fat diet and aerobic exercise on expression of mammalian target of rapamycin/ribosomal protein kinase (mTOR/S6K1) in skeletal muscle of insulin resistant mice.
METHODS: 8-week old, C57BL/6 mice were divided into two groups: which are normal chow and high-fat diet groups, each group has 20 animals feeding by normal chow and high fat diet respectively. 8-weeks later, mice from high fat diet group were proved to have insulin resistance symptoms and after that time point the mice were regrouped. The normal chow group was randomly divided into normal chow diet control group (NC) and normal chow exercise group (NE), and the high fat diet group was randomly divided into high fat diet control group (HC) and high fat diet exercise group (HE). All exercise groups were required to running on treadmill for 6 weeks. Mice were acclimatized to the motorized treadmill by running 60 min per day at the intensity of 75% VO2max five days per week for 6 weeks. By the end of training, we observed the changes of glucose tolerance by oral glucose tolerance test and morphology of pancreatic islet under microscope. Insulin concentration was measured by ELISA. Northern blot and Western blot were performed to detect mTOR, S6K1 (and/or pS6K1-Thr389) mRNA and protein expression in skeletal muscle.
RESULTS: By comparing with NC group, the effect of high-fat diet increased the body weight, fasting serum insulin level and the area of pancreatic islet of the mice in HC group significantly. Furthermore, glucose tolerance was impaired. After 6-week aerobic exercise, above value of descriptive index were significantly decreased in skeletal muscle in HE group. In addition, OGTT was also improved. The expression of mTOR, S6K1 (and/or pS6K1-Thr389) mRNA and protein were significantly decreased.
CONCLUSION: mTOR/S6K1 signaling pathway plays an important role in the development of diet induced insulin resistance. Aerobic exercise attenuates insulin resistance by increasing skeletal muscle insulin sensitivity evidenced by increased energy metabolism decreased activity of mTOR/S6K1 signaling pathway.
