Exercise Training-Induced Improvement in Skeletal Muscle PGC-1α-Mediated Fat Metabolism is Independent of Dietary Glycemic Index

Objective: This study hypothesized that a low-glycemic diet combined with exercise would increase expression of nuclear regulators of fat transport and oxidation in insulin-resistant skeletal muscle. Method: Nineteen subjects (64 +/- 1 y; 34 +/- 1 kg/m(2)) were randomized to receive isocaloric high-glycemic-index (HiGIX; 80 +/- 0.6 units, n = 10) or low-glycemic-index (LoGIX; 40 +/- 0.3 units, n = 9) diets combined with supervised exercise (1 h/d, 5 d/wk at similar to 85% HRmax) for 12 weeks. Insulin sensitivity was determined by hyperinsulinemic-euglycemic clamp. Skeletal muscle biopsies were obtained before and after the intervention to assess fasting gene and protein expression. Results: Weight loss was similar for both groups (9.5 +/- 1.3 kg). Likewise, improvements in insulin sensitivity (P < 0.002) and PPAR gamma (P < 0.002), PGC-1 alpha (P = 0.003), CD36 (P = 0.003), FABP3 (mRNA, P = 0.01 and protein, P = 0.02), and CPT1B (mRNA, P = 0.03 and protein, P = 0.008) expression were similar for both interventions. Increased insulin sensitivity correlated with increased PGC-1 alpha expression (P = 0.04), and increased fasting fat oxidation correlated with increased FABP3 (P = 0.04) and CPT1B (P = 0.05) expression. Conclusions: An exercise/diet program resulting in 8% to 10% weight loss improved insulin sensitivity and key molecular mechanisms in skeletal muscle that are controlled by PGC-1 alpha. These effects were independent of the glycemic index of the diets.