Effects of high-fat diet and regular aerobic exercise on global gene expression in skeletal muscle of C57BL/6 mice.

Exercise training may decrease insulin resistance (IR) and increase glucose tolerance. However, the adaptive responses in skeletal muscle at the molecular and genetic level have not been clearly understood. Here we used oligonucleotide microarray analysis to dissect the effects of high-fat diet (HFD) and regular aerobic exercise on global gene expression in the skeletal muscle of C57BL/6 mice. C57BL/6 male mice (n = 40) were fed with normal chow (n = 20) and HFD (n = 20) for 8 weeks. The animals were then divided into 1 of 4 intervention groups: groups of mice fed with normal chow and HFD accompanied with 6-week treadmill running (60 min/d) at 75% maximum oxygen consumption (NE and HE) and their sedentary control groups (NC and HC). Oligonucleotide microarray was applied to analyze the effect of aerobic exercise and HFD at the transcriptional level, and selected genes were confirmed by real-time polymerase chain reaction. Our data showed that 6 weeks of aerobic exercise improved the plasma lipid profile and reversed the glucose intolerance induced by HFD. A set of 503 genes was differentially expressed in samples of HC mice as compared with those of the NC group. Forty of those genes were identified as involved in the process of aerobic exercise ameliorating IR by comparing the changes in expression profiles between the HE and HC groups. These changes include genes involved in metabolism, defense, and inflammation and genes of unknown function. Aerobic exercise training is able to ameliorate IR of mice maintained with HFD. The biochemical pathways involved in ameliorating IR identified in this study may represent potential targets for the treatment of IR.