title: Skeletal muscle myofibrillar and sarcoplasmic protein synthesis rates are affected differently by altitude-induced hypoxia in native lowlanders.
abstract: As a consequence to hypobaric hypoxic exposure skeletal muscle atrophy is often reported. The underlying mechanism has been suggested to involve a decrease in protein synthesis in order to conserve O(2). With the aim to challenge this hypothesis, we applied a primed, constant infusion of 1-(13)C-leucine in nine healthy male subjects at sea level and subsequently at high-altitude (4559 m) after 7-9 days of acclimatization. Physical activity levels and food and energy intake were controlled prior to the two experimental conditions with the aim to standardize these confounding factors. Blood samples and expired breath samples were collected hourly during the 4 hour trial and vastus lateralis muscle biopsies obtained at 1 and 4 hours after tracer priming in the overnight fasted state. Myofibrillar protein synthesis rate was doubled; 0.041±0.018 at sea-level to 0.080±0.018%⋅hr(-1) (p<0.05) when acclimatized to high altitude. The sarcoplasmic protein synthesis rate was in contrast unaffected by altitude exposure; 0.052±0.019 at sea-level to 0.059±0.010%⋅hr(-1) (p>0.05). Trends to increments in whole body protein kinetics were seen: Degradation rate elevated from 2.51±0.21 at sea level to 2.73±0.13 µmol⋅kg(-1)⋅min(-1) (p = 0.05) at high altitude and synthesis rate similar; 2.24±0.20 at sea level and 2.43±0.13 µmol⋅kg(-1)⋅min(-1) (p>0.05) at altitude. We conclude that whole body amino acid flux is increased due to an elevated protein turnover rate. Resting skeletal muscle myocontractile protein synthesis rate was concomitantly elevated by high-altitude induced hypoxia, whereas the sarcoplasmic protein synthesis rate was unaffected by hypoxia. These changed responses may lead to divergent adaptation over the course of prolonged exposure.
authors.affiliation: Department of Orthopaedic Surgery M and Institute of Sports Medicine, Bispebjerg Hospital, and Faculty of Health Sciences, Center of Healthy Ageing, University of Copenhagen, Copenhagen, Denmark. L.Holm.isotope@gmail.com
authors.forename: Lars
authors.initials: L
authors.lastname: Holm
authors.forename: Mads Lyhne
authors.initials: ML
authors.lastname: Haslund
authors.forename: Paul
authors.initials: P
authors.lastname: Robach
authors.forename: Gerrit
authors.initials: G
authors.lastname: van Hall
authors.forename: Jose A L
authors.initials: JA
authors.lastname: Calbet
authors.forename: Bengt
authors.initials: B
authors.lastname: Saltin
authors.forename: Carsten
authors.initials: C
authors.lastname: Lundby
mesh_terms: D000064:Acclimatization / Q000502:physiology; D000328:Adult; D000531:Altitude; D001706:Biopsy; D001784:Blood Gas Analysis; D001823:Body Composition; D001835:Body Weight; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007700:Kinetics; D007930:Leucine / Q000737:chemistry; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology* / Q000473:pathology; D009210:Myofibrils / Q000378:metabolism*; D010100:Oxygen / Q000737:chemistry
chemical_list: D009124:Muscle Proteins; D007930:Leucine; D010100:Oxygen