Exercise training-induced improvement in skeletal muscle PGC-1α-mediated fat metabolism is independent of dietary glycemic index

Research output: Contribution to journalArticle


  • Anny Mulya
  • Jacob M Haus
  • Karen R Kelly
  • Steven K Malin
  • Michael Rocco
  • Hope Barkoukis
  • John P Kirwan

Colleges, School and Institutes

External organisations

  • Department of Preventive Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio.
  • Department of Nutrition, School of Medicine, Case Western Reserve University, Cleveland, Ohio.
  • Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.


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 ∼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 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 8% to 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.


Original languageEnglish
Pages (from-to)721-729
Number of pages9
Issue number4
Publication statusPublished - 28 Mar 2017


  • Journal Article