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Disuse atrophy delays and reduces amino acid induced activation of key translational signaling proteins in humans

We aimed to determine the effect of muscle disuse on activation by mixed amino acid (AA) feeding of three anabolic signaling proteins: mTOR, eIF2Bε and p70s6k. 10 men and 2 women wore an immobilizing knee brace for 14d, reducing muscle by CSA (5±1%, P<0.001). Subjects then received infusions of mixed AA at either 44 mg kg−1h−1 or 261 mg kg−1h−1. Quadriceps biopsies were taken from both legs when fasted and fed (1, 2, 4 h). After 1 h AA infusion phosphorylation of mTOR (Ser2448), eIF2Bε (Ser 539) and p70s6k (Thr389) in the non‐immobilized leg increased by 35–56% (P<0.05), with a return to baseline by 2 h (p70s6k) or 4 h (mTOR, eIF2Bε). In the immobilized leg mTOR phosphorylation did not significantly increase at all after AA infusion whereas phosphorylation of eIF2Bε increased by only 22% at 2 h (P<0.05); phosphorylation of p70s6k increased by only 32 % at 1 h (P<0.05), but remained elevated until 4 h. p70s6k phosphorylation was 22 % higher (P=0.05) in the immobilized leg in the fasted state. These findings, together with an observed depressed AA‐induced muscle protein synthetic response, suggest a dampened response of the underlying translational control mechanisms with disuse atrophy in humans. We propose that a reduction in the feeding‐induced stimulation of muscle protein synthesis is of major importance in causing muscle loss with disuse in humans. Support: NSERC, CIHR, UK BBSRC, and EC EXEGENESIS