Impaired exercise training-induced muscle fiber hypertrophy and Akt/mTOR pathway activation in hypoxemic patients with COPD

F. Costes, H.R. Gosker, L. Feasson, M. Desgeorges, M.C. Kelders, J. Castells, A.M. Schols, D.G. Freyssenet

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Exercise training (ExTr) is largely used to improve functional capacity of chronic obstructive pulmonary disease (COPD) patients. However, ExTr partially restores muscle function in COPD patients, 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 COPD patients. Vastus lateralis muscle biopsies were obtained from normoxemic (n = 15; resting arterial PO2 = 68.5 +/- 1.5 mm Hg) and hypoxemic (n = 8; resting arterial PO2 = 57.0 +/- 1.0 mm Hg) COPD patients before and after a 2 month-ExTr program. ExTr induced a significant increase in exercise capacity both in normoxemic and hypoxemic COPD patients. 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 only increased in normoxemic patients. Expression of atrogenes (MuRF1, MAFbx/Atrogin-1) and autophagy-related genes (Beclin, LC3, Bnip, Gabarapl) remained unchanged in both groups. The phosphorylation level of Akt (Ser473), GSK-3beta (Ser9) and p70S6k (Thr389), which was non-significantly increased in normoxemic patients in response to ExTr, was significantly decreased in hypoxemic patients. We further showed on C2C12 myotubes that hypoxia completely prevented IGF-1-induced phosphorylation of Akt, GSK-3beta and p70S6K. Together, our observations suggest a role for hypoxemia in the adaptive response of skeletal muscle of COPD patients to ExTr.
Original languageEnglish
Pages (from-to)1040-1049
Number of pages10
JournalJournal of Applied Physiology
Volume118
Issue number8
DOIs
Publication statusPublished - 15 Apr 2015

Keywords

  • COPD
  • skeletal muscle
  • hypoxia
  • exercise training
  • OBSTRUCTIVE PULMONARY-DISEASE
  • CHRONIC RESPIRATORY-FAILURE
  • FOXO TRANSCRIPTION FACTORS
  • SKELETAL-MUSCLE
  • UBIQUITIN-PROTEASOME
  • HYPOBARIC HYPOXIA
  • ENZYME-ACTIVITIES
  • GENE-EXPRESSION
  • REHABILITATION
  • ATROPHY

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