Decreased Mitochondrial Dynamics Is Associated with Insulin Resistance, Metabolic Rate, and Fitness in African Americans.

Abstract

African American women (AAW) have a higher incidence of insulin resistance and are at a greater risk for the development of obesity and type 2 diabetes than Caucasian women (CW). Although several factors have been proposed to mediate these racial disparities, the mechanisms remain poorly defined. We previously demonstrated that sedentary lean AAW have lower peripheral insulin sensitivity, reduced maximal aerobic fitness (VO2max), and lower resting metabolic rate (RMR) than CW. We have also demonstrated that skeletal muscle mitochondrial respiration is lower in AAW and appears to play a role in these racial differences. The goal of this study was to assess mitochondrial pathways and dynamics to examine the potential mechanisms of lower insulin sensitivity, RMR, VO2max, and mitochondrial capacity in AAW. To achieve this goal, we assessed several mitochondrial pathways in skeletal muscle using gene array technology and semiquantitative protein analysis. We report alterations in mitochondrial pathways associated with inner membrane small molecule transport genes, fusion-fission, and autophagy in lean AAW. These differences were associated with lower insulin sensitivity, RMR, and VO2max. Together these data suggest that the metabolic racial disparity of insulin resistance, RMR, VO2max, and mitochondrial capacity may be mediated by perturbations in mitochondrial pathways associated with membrane transport, fission-fusion, and autophagy. The mechanisms contributing to these differences remain unknown.