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

OBJECTIVE: We 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 yrs; 34±1 kg/m(2)) were randomized to receive isocaloric high- (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 ~85% HR(max)) 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 PPARγ (P<0.002), PGC-1α (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-1α 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 an 8–10% weight loss improved insulin sensitivity and key molecular mechanisms in skeletal muscle that are controlled by PGC-1α. These effects were independent of the glycemic index of the diets.