Exercise training improves insulin sensitivity in skeletal muscle and increases mitochondrial function. These improvements are due, in part, to an increase in expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha). The effect of exercise training on epigenetic factors, such as DNA methylation remains elusive. The aim of this study was to determine whether an 8-week exercise training alters DNA methylation of PGC-1 alpha. Fourteen participants (5M/9F; age 34.2±3.0 years) were studied before and after 8-weeks of supervised exercise training (60% of VO2peak for 20 minutes, 3 times per week; gradually increased to 70% of VO2peak for 45 minutes, 4 times per week). Euglycemic hyperinsulinemic clamps in combination with vastus lateralis muscle biopsies were obtained before and after the exercise training. Training increased peak aerobic capacity (VO2peak) from 31.9±1.0 to 36.5±1.4 ml∙min-1∙kg FFM-1 (P = 0.013) and improved insulin sensitivity from 7.0±2.1 to 9.2±2.3 ml·kg FFM−1·min−1. Genomic DNA was extracted and pyrosequencing methylation analysis was performed on CpG -816 and -783 bp upstream transcription start site (TSS). Methylation analysis revealed a significantly decreased methylation at CpG -816 bp following exercise (pre = 16.8±0.9 % versus post = 14.2±0.5 %, P = 0.035). For CpG -783 bp, methylation did not change following exercise (pre = 11±0.6 % versus post = 11.5±0.7 %, P = NS). Our results showed that exercise training improved insulin sensitivity and peak aerobic capacity. In addition, we provide evidence that exercise training alters PGC-1 alpha methylation at CpG -816 bp. We propose that the increased response of insulin action in muscle following exercise training is due, in part, to epigenetic modifications.


S. Lee: None. L. Garcia: None. A.D. Leon: None. R. Zapata Bustos: None. B. Campos: None. J.A. Krentzel: None. L. Mandarino: None. D.K. Coletta: None.


National Institutes of Health (R01DK094013)

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