Journal
JOURNAL OF APPLIED PHYSIOLOGY
Volume 118, Issue 8, Pages 1040-1049Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/japplphysiol.00557.2014
Keywords
COPD; skeletal muscle; hypoxia; exercise training
Categories
Funding
- Ministere de la Sante, France
- Association Lyonnaise de Logistique Post-hospitaliere
- European Respiratory Society
- Netherlands Asthma Foundation [3.2.05.038]
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Exercise training (ExTr) is largely used to improve functional capacity in patients with chronic obstructive pulmonary disease (COPD). However, ExTr only partially restores muscle function in patients with COPD, suggesting that confounding factors may limit the efficiency of ExTr. In the present study, we hypothesized that skeletal muscle adaptations triggered by ExTr could be compromised in hypoxemic patients with COPD. Vastus lateralis muscle biopsies were obtained from patients with COPD who were either normoxemic (n = 15, resting arterial PO2 = 68.5 +/- 1.5 mmHg) or hypoxemic (n = 8, resting arterial PO2 = 57.0 +/- 1.0 mmHg) before and after a 2-mo ExTr program. ExTr induced a significant increase in exercise capacity both in normoxemic and hypoxemic patients with COPD. However, ExTr increased citrate synthase and lactate dehydrogenase enzyme activities only in skeletal muscle of normoxemic patients. Similarly, muscle fiber cross-sectional area and capillary-to-fiber ratio were increased only in patients who were normoxemic. Expression of atrogenes (MuRF1, MAFbx/Atrogin-1) and autophagy-related genes (Beclin, LC3, Bnip, Gabarapl) remained unchanged in both groups. Phosphorylation of Akt (Ser473), GSK-3 beta (Ser9), and p70S6k (Thr389) was nonsignificantly increased in normoxemic patients in response to ExTr, but it was significantly decreased in hypoxemic patients. We further showed on C2C12 myotubes that hypoxia completely prevented insulin-like growth factor-1-induced phosphorylation of Akt, GSK-3 beta, and p70S6K. Together, our observations suggest a role for hypoxemia in the adaptive response of skeletal muscle of patients with COPD in an ExTr program.
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