Muscle mitochondrial oxidative phosphorylation activity, but not content, is altered with abdominal obesity in sedentary men: synergism with changes in insulin sensitivity.

Abstract

Abdominal obesity is a major risk factor for muscle insulin resistance. Mitochondria may play a key role in this etiology. Changes in muscle mitochondrial content and function were examined according to abdominal obesity and insulin sensitivity in men. The descriptive MitHyCal study was conducted on the general population of Clermont-Ferrand, France. Forty-two healthy sedentary men (41.7 +/- 4.3 yr) were divided into four groups according to waist circumference: 87 cm or less (group 1, n = 10); 88-93 cm (group 2, n = 12); 94-101 cm (group 3, n = 10); and 102 cm or greater (group 4, n = 10). Plasma metabolic check-up was performed, and insulin sensitivity index was calculated from glucose and insulin responses to a 3-h oral glucose tolerance test. Muscle biopsies were obtained to assess mitochondrial content, oxidative phosphorylation activity, and superoxide anion (reactive oxygen species) production. Assessment of muscle mitochondrial content and function was planned before data collection began. Abdominal obesity was negatively correlated to insulin sensitivity index (r = -0.39; P < 0.01), and only group 4 was insulin-resistant (P < 0.05). There were no between-group differences in muscle mitochondrial content and maximal activity of key oxidative enzymes. In contrast, muscle mitochondrial ADP-stimulated respiration rate was 24% higher in groups 2 and 3 compared to groups 1 and 4 (P < 0.05). Mitochondrial ATP and reactive oxygen species production rates were 27 and 48% lower in group 4 than in group 1 (P < 0.05). Abdominal obesity is associated with alterations in intrinsic muscle mitochondrial function but not content. These adaptations mainly result in reduced mitochondrial ATP production rate in response to insulin resistance.