title: Effects of hypoxia on muscle protein synthesis and anabolic signaling at rest and in response to acute resistance exercise.
abstract: Chronic reductions in tissue O(2) tension (hypoxia) are associated with muscle atrophy and blunted hypertrophic responses to resistance exercise (RE) training. However, the effect of hypoxia on muscle protein synthesis (MPS) at rest and after RE is unknown. In a crossover study, seven healthy men (21.4 ± 0.7 yr) performed unilateral leg RE (6 × 8 repetitions at 70% 1-repetition maximum) under normoxic (20.9% inspired O(2)) and normobaric hypoxic (12% inspired O(2) for 3.5 h) postabsorptive conditions. Immediately after RE the rested leg was biopsied, and a primed continuous infusion of [1,2-(13)C(2)]leucine was maintained for 2.5 h before final biopsies from both legs to measure tracer incorporation and signaling responses (i.e., ribosomal S6 kinase 1). After 3.5 h of hypoxia, MPS was not different from normoxia in the rested leg (normoxia 0.033 ± 0.016 vs. hypoxia 0.043 ± 0.016%/h). MPS increased significantly from baseline 2.5 h after RE in normoxia (0.033 ± 0.016 vs. 0.104 ± 0.038%/h) but not hypoxia (0.043 ± 0.016 vs. 0.060 ± 0.063%/h). A significant linear relationship existed between MPS 2.5 h after RE in hypoxia and mean arterial blood O(2) saturation during hypoxia (r(2) = 0.49, P = 0.04). Phosphorylation of p70S6K(Thr389) remained unchanged in hypoxia at rest but increased after RE in both normoxia and hypoxia (2.6 ± 1.2-fold and 3.4 ± 1.1-fold, respectively). Concentrations of the hypoxia-responsive mTOR inhibitor regulated in development and DNA damage-1 were unaltered by hypoxia or RE. We conclude that normobaric hypoxia does not reduce MPS over 3.5 h at rest but blunts the increased MPS response to acute RE to a degree dependent on extant SpO(2).
authors.affiliation: University of Nottingham, School of Graduate Entry Medicine and Health, Derby, UK. timothy.etheridge@nottingham.ac.uk
authors.forename: Timothy
authors.initials: T
authors.lastname: Etheridge
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Atherton
authors.forename: Daniel
authors.initials: D
authors.lastname: Wilkinson
authors.forename: Anna
authors.initials: A
authors.lastname: Selby
authors.forename: Debbie
authors.initials: D
authors.lastname: Rankin
authors.forename: Nick
authors.initials: N
authors.lastname: Webborn
authors.forename: Kenneth
authors.initials: K
authors.lastname: Smith
authors.forename: Peter W
authors.initials: PW
authors.lastname: Watt
mesh_terms: D018592:Cross-Over Studies; D015444:Exercise / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010101:Oxygen Consumption / Q000502:physiology; D010766:Phosphorylation / Q000502:physiology; D055070:Resistance Training; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism; D055815:Young Adult
chemical_list: D009124:Muscle Proteins; D038762:Ribosomal Protein S6 Kinases, 70-kDa