Bed rest and resistive vibration exercise unveil novel links between skeletal muscle mitochondrial function and insulin resistance
Résumé
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
⋅
O2peak) (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.