Enhanced fat oxidation through physical activity is associated with improvements in insulin sensitivity in obesity

Skeletal muscle insulin resistance entails dysregulation of both glucose and fatty acid metabolism. This study examined whether a combined intervention of physical activity and weight loss influences fasting rates of fat oxidation and insulin-stimulated glucose disposal. Obese (BMI >30 kg/m(2)) volunteers (9 men and 16 women) without diabetes, aged 39 +/- 4 years, completed 16 weeks of moderate-intensity physical activity combined with caloric reduction. Body composition was determined by dual-energy X-ray absorptiometry and computed tomography. Glucose disposal rates (R(d)) were measured during euglycemic hyperinsulinemia (40 mU x m(-2) x min(-1)), and substrate oxidation was determined via indirect calorimetry. Fat mass and regional fat depots were reduced and VO(2max) improved by 19%, from 38.8 +/- 1.2 to 46.0 +/- 1.0 ml x kg fat-free mass (FFM)(-1) x min(-1) (P < 0.05). Insulin sensitivity improved 49 +/- 10% (6.70 +/- 0.40 to 9.51 +/- 0.51 mg x min(-1) x kg FFM(-1); P < 0.05). Rates of fat oxidation following an overnight fast increased (1.16 +/- 0.06 to 1.36 +/- 0.05 mg x min(-1) x kg FFM(-1); P < 0.05), and the proportion of energy derived from fat increased from 38 to 52%. The strongest predictor of the improved insulin sensitivity was enhanced fasting rates of fat oxidation, accounting for 52% of the variance. In conclusion, exercise combined with weight loss enhances postabsorptive fat oxidation, which appears to be a key aspect of the improvement in insulin sensitivity in obesity.