Bed rest and resistive vibration exercise unveil novel links between skeletal muscle mitochondrial function and insulin resistance

Aims/hypothesis Physical inactivity has broad implications for human disease including insulin resistance, sarcopenia and obesity. The present study tested the hypothesis that (1) impaired mitochondrial respiration is linked with blunted insulin sensitivity and loss of muscle mass in healthy young men, and (2) resistive vibration exercise (RVE) would mitigate the negative metabolic effects of bed rest. Methods Participants (n = 9) were maintained in energy balance during 21 days of bed rest with RVE and without (CON) in a crossover study. Mitochondrial respiration was determined by high-resolution respirometry in permeabilised fibre bundles from biopsies of the vastus lateralis. A hyperinsulinaemic-euglycaemic clamp was used to determine insulin sensitivity, and body composition was assessed by dual-energy x-ray absorptiometry (DEXA). Results Body mass (-3.2 +/- 0.5 kg vs -2.8 +/- 0.4 kg for CON and RVE, respectively, p < 0.05), fat-free mass (-2.9 +/- 0.5 kg vs -2.7 +/- 0.5 kg, p < 0.05) and peak oxygen consumption ((V) over dotO(2peak)) (10-15%, p < 0.05) were all reduced following bed rest. Bed rest decreased insulin sensitivity in the CON group (0.04 +/- 0.002 mg kgFFM(-1) [pmol l(-1)] min(-1) vs 0.03 +/- 0.002 mg kgFFM(-1) [pmol l(-1)] min(-1) for baseline vs post-CON), while RVE mitigated this response (0.04 +/- 0.003 mg kgFFM(-1) [pmol l(-1)] min(-1)). Mitochondrial respiration (oxidative phosphorylation and electron transport system capacity) decreased in the CON group but not in the RVE group when expressed relative to tissue weight but not when normalised for citrate synthase activity. LEAK respiration, indicating a decrease in mitochondrial uncoupling, was the only component to remain significantly lower in the CON group after normalisation for citrate synthase. This was accompanied by a significant decrease in adenine nucleotide translocase protein content. Conclusions/interpretation Reductions in muscle mitochondrial respiration occur concomitantly with insulin resistance and loss of muscle mass during bed rest and may play a role in the adaptations to physical inactivity. Significantly, we show that RVE is an effective strategy to partially prevent some of the deleterious metabolic effects of bed rest.