Skeletal Muscle Myofibrillar and Sarcoplasmic Protein Synthesis Rates Are Affected Differently by Altitude-Induced Hypoxia in Native Lowlanders

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 O2. With the aim to challenge this hypothesis, we applied a primed, constant infusion of 1-13C-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

Venous plasma KIC and muscle protein bound leucine enrichments.

<p>Enrichments in the precursor; venous plasma alpha-¹³C-ketoisocaproic acid (KIC) in percent tracer-to-tracee ratio (TTR) at time points every hour throughout the FSR-determination period. An effect of time (p<0.001) and altitude (p<0.05) appeared. Isotope ratios of ¹³C/¹²C in leucine liberated from the myofibrillar and sarcoplasmic protein fractions, respectively, in the muscle tissue at 1 and 4 hours at sea level and at altitude. N = 8 and values are mean ± SEM.</p

Muscle protein fractional synthesis rate.

<p>Resting and fasting fractional synthesis rate [%·hr⁻¹] of A) myofibrillar proteins and B) sarcoplasmic proteins at sea level and after 7–9 days of acclimatization to 4559 m altitude. N = 8 and values are mean ± SEM.</p

Venous plasma hormonal concentrations.

<p>Venous plasma concentrations of insulin [µlU·mL⁻¹], human growth hormone [hGH; µlU·mL⁻¹], cortisol [ng·mL⁻¹], testosterone [pg·mL⁻¹], and insulin like growth factor-1 [ng·mL⁻¹] in male subjects at sea level and after 7–9 days exposure to high altitude. N = 9 and values are mean ± SEM.</p

Whole body leucine turnover.

<p>Whole body leucine rate of appearance (Ra), leucine oxidation, and non-oxidative leucine rate of disappearance (Rd) [µmol⋅kg⁻¹⋅min⁻¹] in male subjects at sea level and after 7–9 days exposure to high altitude. N = 6, and values are mean ± SEM.</p