Role of exercise and rapamycin on the expression of energy metabolism genes in liver tissues of rats fed a high-fat diet

The mTOR pathway serves an important role in the development of insulin resistance induced by obesity. Exercise improves obesity-associated insulin resistance and hepatic energy metabolism; however, the precise mechanism of this process remains unknown. Therefore, the present study investigated the role of rapamycin, an inhibitor of mTOR, on exercise-induced expression of hepatic energy metabolism genes in rats fed a high-fat diet (HFD). A total of 30 male rats were divided into the following groups: Normal group (n=6) fed chow diets and HFD group (n=24) fed an HFD for 6 weeks. The HFD rats performed exercise adaptation for 1 week and were randomly divided into the four following groups (each containing six rats): i) Group of HFD rats with sedentary (H group); ii) group of HFD rats with exercise (HE group); iii) group of HFD rats with rapamycin (HR group); and iv) group of HFD rats with exercise and rapamycin (HER group). Both HE and HER rats were placed on incremental treadmill training for 4 weeks (from week 8–11). Both HR and HER rats were injected with rapamycin intraperitoneally at the dose of 2 mg/kg once a day for 2 weeks (from week 10–11). All rats were sacrificed following a 12–16 h fasting period at the end of week 11. The levels of mitochondrial and oxidative enzyme activities, as well as of the expression of genes involved in energy metabolism were assessed in liver tissues. Biochemical assays and oil red staining were used to assess the content of hepatic triglycerides (TGs). The results indicated that exercise, but not rapamycin, reduced TG content in the liver of HFD rats. Further analysis indicated that rapamycin reduced the activity of cytochrome c oxidase, but not the activities of succinate dehydrogenase and β-hydroxyacyl-CoA dehydrogenase in the liver of HFD rats. Exercise significantly upregulated the mRNA expression of peroxisome proliferator-activated receptor γ coactivator 1 β, while rapamycin exhibited no effect on the mRNA expression levels of hepatic transcription factors associated with energy metabolism enzymes in the liver of HFD rats. Collectively, the results indicated that exercise reduced TG content and upregulated mitochondrial metabolic gene expression in the liver of HFD rats. Moreover, this mechanism may not involve the mTOR pathway.