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J Appl Physiol 100: 1258-1266, 2006; doi:10.1152/japplphysiol.00359.2005
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Exercise training in normobaric hypoxia in endurance runners. III. Muscular adjustments of selected gene transcripts

Joffrey Zoll,1 Elodie Ponsot,2 Stéphane Dufour,2 Stéphane Doutreleau,2 Renée Ventura-Clapier,3 Michael Vogt,1 Hans Hoppeler,1 Ruddy Richard,2 and Martin Flück1

1Department of Anatomy, University of Bern, 3012 Bern, Switzerland; 2Service de Physiologie Clinique et des Explorations Fonctionnelles Respiratoires et de l'Exercice, Département de Physiologie Équipe d'Accueil 3072, Strasbourg, France; and 3Cardiologie Cellulaire et Moléculaire U-446 Institut National de la Santé et de la Recherche Médicale, Faculté de Pharmacie, Université Paris-Sud, Châtenay-Malabry, France

Submitted 29 March 2005 ; accepted in final form 29 August 2005

We hypothesized that specific muscular transcript level adaptations participate in the improvement of endurance performances following intermittent hypoxia training in endurance-trained subjects. Fifteen male high-level, long-distance runners integrated a modified living low-training high program comprising two weekly controlled training sessions performed at the second ventilatory threshold for 6 wk into their normal training schedule. The athletes were randomly assigned to either a normoxic (Nor) (inspired O2 fraction = 20.9%, n = 6) or a hypoxic group exercising under normobaric hypoxia (Hyp) (inspired O2 fraction = 14.5%, n = 9). Oxygen uptake and speed at second ventilatory threshold, maximal oxygen uptake (VO2 max), and time to exhaustion (Tlim) at constant load at VO2 max velocity in normoxia and muscular levels of selected mRNAs in biopsies were determined before and after training. VO2 max (+5%) and Tlim (+35%) increased specifically in the Hyp group. At the molecular level, mRNA concentrations of the hypoxia-inducible factor 1{alpha} (+104%), glucose transporter-4 (+32%), phosphofructokinase (+32%), peroxisome proliferator-activated receptor gamma coactivator 1{alpha} (+60%), citrate synthase (+28%), cytochrome oxidase 1 (+74%) and 4 (+36%), carbonic anhydrase-3 (+74%), and manganese superoxide dismutase (+44%) were significantly augmented in muscle after exercise training in Hyp only. Significant correlations were noted between muscular mRNA levels of monocarboxylate transporter-1, carbonic anhydrase-3, glucose transporter-4, and Tlim only in the group of athletes who trained in hypoxia (P < 0.05). Accordingly, the addition of short hypoxic stress to the regular endurance training protocol induces transcriptional adaptations in skeletal muscle of athletic subjects. Expressional adaptations involving redox regulation and glucose uptake are being recognized as a potential molecular pathway, resulting in improved endurance performance in hypoxia-trained subjects.

athletes; messenger ribonucleic acid; redox regulation; glucose uptake


Address for reprint requests and other correspondence: Martin Flück, Dept. of Anatomy, Univ. of Bern, Bühlstrasse 26, 3000 Bern 9, Switzerland (e-mail: flueck{at}ana.unibe.ch)




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