Exercise Is Required to Improve Mitochondrial Respiratory Capacity in Skeletal Muscle of Older Obese Subjects during Calorie Restriction–Induced Weight Loss to Improve Insulin Sensitivity

Abstract

Calorie restriction has been shown to have “anti-aging” effects in animal models, and calorie restriction-induced weight loss (CRWL) and exercise can both improve insulin sensitivity. The aim of this study was to investigate the effect of 6-month diet-induced weight loss intervention with or without the addition of exercise training on skeletal muscle mitochondrial respiratory capacity and IS. Methods: Forty-four older adults with obesity were randomized to one of the following 6-month intervention: Health education (CON: n=14, age=70±4 years, BMI=34±5kg/m2), Diet induced weight-loss (DIWL: n=14, age=70±4 years, BMI=36±5kg kg/m2), or Weight-loss and exercise (WLEX: n=16, age=66±3 years, BMI=37±5kg/m2). CRWL and WLEX participants had a goal of 10% weight-loss through calorie restriction. Subjects in the WLEX group completed a supervised exercise program. Mitochondrial respiratory capacity of permeabilized myofibers from biopsies was evaluated by high-resolution respirometry. Complex I+II supported maximal oxidative phosphorylation (OXPHOS), and maximal uncoupled respiration were evaluated. IS was determined by hyperinsulinemic euglycemic clamps. Results: IS improved in both CRWL (10.4%) and WLEX (50%) compared to CON (0.7%). However, while mitochondrial respiration was unchanged in the CON and CRWL groups after the 6-month intervention (p>0.05), subjects in the WLEX group presented an increased maximal OXPHOS (PRE: 50.7±10.1 vs. POST: 72.6±17.9 pmol/s*mg) and uncoupled respiration (PRE: 57.2±10.5 vs. POST: 79.6±19.3 pmol/s*mg) after the exercise training. Conclusions: Despite weight loss and exercise both improving insulin sensitivity, exercise is required to improve mitochondrial respiratory capacity in skeletal muscle of older obese human subjects undergoing calorie restriction-induced weight loss. Disclosure G. Distefano: None. R. Standley: None. E.A. Carnero: None. P.M. Coen: None. R.B. Vega: None. B.H. Goodpaster: None.