Combined exercise and calorie restriction therapies restore contractile and mitochondrial functions in skeletal muscle of obese-insulin resistant rats.

Abstract

A combined exercise training and calorie-restriction program is the mainstream treatment of obesity. However, the effect of the dual-action program on mitochondrial function in skeletal muscles has not yet been clarified. The aim of this study was to determine if the combined program, rather than a single program, restored both lost muscle activity and mitochondrial function in obesity. The study included 30 female Wistar rats. Six rats fed a normal diet for 27 wk were used as the control group. The remaining 24 rats were fed a high-fat diet (HFD) for 27 wk. At week 20, the HFD rats were divided into the following four groups: sedentary lifestyle, endurance exercise five times per week, 60% of calorie restriction (CR) per day, and combined exercise training and CR. All conditions were maintained for 7 wk. We found that HFD-fed rats without therapy developed obese insulin resistance (IR) and impaired function of skeletal muscles. Skeletal muscles of the HFD-fed rats without therapy also exhibited early fatigability; impaired mitochondrial function, as indicated by increased reactive oxygen species production, membrane depolarization, and swelling; reduced mitochondrial dynamics as indicated by increased phosphorylation of DRP1 and decreased MFN2 expression; diminished mitochondrial biogenesis, as shown by decreased PGC1α and CPT1 expression; and increased apoptosis. Both exercise and CR in HFD-fed rats equally attenuated the impairment of muscle functions. However, combined therapies in HFD-fed rats restored functions of skeletal muscles. These findings reinforce the synergistic beneficial effects of combined exercise and CR on skeletal muscles of HFD-fed rats.