Sedentary Behavior Inversely Relates to Insulin Sensitivity and Mitochondrial Oxidative Capacity in Inactive Obese Adults

Abstract

Sedentary time (ST) is associated with increased risk for insulin resistance, metabolic syndrome, and type 2 diabetes. The impact of ST on insulin sensitivity and muscle mitochondrial oxidative capacity, key mediators of the aforementioned metabolic diseases, is not fully understood. PURPOSE: We sought to determine the impact of ST on insulin sensitivity and muscle oxidative capacity in obese, physically inactive adults. METHODS: We studied 19 inactive, obese (35+1 kg/m2), middle aged (54+1 y) adults. We measured insulin sensitivity using a standardized two-stage hyperinsulinemic-eugIycemic clamp. In isolated vastus lateralis muscle mitochondria, we measured state-3 oxygen flux rates (JO2) by high-resolution respirometry using substrates for complex I, I+II, and II. Finally, we measured ST (<100 counts per min) and time spent in moderate to vigorous physical activity (MVPA, >2020 counts per min) using accelerometry. We used multivariate regression analysis to test for associations between ST and insulin sensitivity and muscle oxidative capacity adjusted for age and MVPA. RESULTS: Data are presented as mean + SEM. The average steady-state glucose infusion rate to maintain euglycemia during the high-dose insulin infusion was 8.4+1 mg/kgFFM/min. The average JO2 were 232 + 16 pmols/s/ml (complex I) and 307+16 pmols/s/ml (complex II). The average wear-time adjusted times spent in ST and MVPA were 570+30 min/d (9.5+0.5 h/d) and 20.4+0.5 min/d. The partial correlations between ST and the average glucose infusion rate and JO2 rates adjusted for age and MVPA were -0.62 (p=0.007), -0.51 (p=0.027, for complex I), and -0.32 (p=0.21, for complex II). CONCLUSION: ST inversely correlates with insulin sensitivity and complex I mediated muscle oxidative capacity in inactive, middle-aged, obese adults when adjusted for age and MVPA. We propose that reducing ST will improve insulin sensitivity and muscle oxidative capacity.