Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion.
Level 3 - non-randomized controlled study
Prospective within-subject controlled physiological trial using the contralateral limb as control without randomization.
PubMed 18955382 · doi:10.1113/jphysiol.2008.160333
What was done
Twelve young healthy adults (10 men, 2 women, age 21 ± 1 years, body weight 80.2 ± 4.0 kg) underwent 14 days of unilateral knee immobilization with the contralateral leg serving as a non-immobilized control. Quadriceps myofibrillar protein synthesis (MPS) was measured in both legs in the post-absorptive state and during intravenous amino acid infusion (10% Primene) at low (43 mg/kg/h) or high (261 mg/kg/h) doses. Quadriceps muscle cross-sectional area (MRI), peak isometric torque, anabolic signaling phosphorylation, and polyubiquitinated protein content were also assessed.
What was found
In the immobilized leg, muscle cross-sectional area decreased by -5.0 ± 1.2% and peak isometric torque decreased by -25 ± 3% (both P < 0.005), with no changes in the non-immobilized leg (P > 0.6). Basal post-absorptive MPS was 27% lower in the immobilized leg (0.027 ± 0.003%/h) compared to the non-immobilized leg (0.037 ± 0.003%/h; P < 0.001). Amino acid infusion stimulated MPS in both legs, but the response was blunted in the immobilized limb: at 4 h, MPS was higher in the non-immobilized leg by +54 ± 12% at the low dose and +68 ± 17% at the high dose (both P < 0.001). Phosphorylation of focal adhesion kinase (Tyr576/577) declined with immobilization (P < 0.05), whereas polyubiquitinated protein content remained unchanged.
Why it matters
This study shows that disuse muscle atrophy is primarily driven by reduced basal muscle protein synthesis and blunted sensitivity to hyperaminoacidemia, which cannot be rescued simply by increasing amino acid availability.
Limits
The sample size was small (n = 12) with an uneven sex distribution (10 men, 2 women) and tested only young, healthy adults. Amino acids were administered intravenously rather than through oral protein feeding, and muscle protein breakdown rates were not directly quantified.
Cited by
- supports A study by Alisa Glover and Stuart Phillips showed that branched-chain amino acid concentrations increase in the intracellular space of muscle tissue.