Declines in muscle protein synthesis account for short-term muscle disuse atrophy in humans in the absence of increased muscle protein breakdown.

ABSTRACT

BACKGROUND: We determined the short-term (i.e. 4 days) impacts of disuse atrophy in relation to muscle protein turnover [acute fasted-fed muscle protein synthesis (MPS)/muscle protein breakdown (MPB) and integrated MPS/estimated MPB]. METHODS: Healthy men (N = 9, 22 ± 2 years, body mass index 24 ± 3 kg m-2 ) underwent 4 day unilateral leg immobilization. Vastus lateralis (VL) muscle thickness (MT) and extensor strength and thigh lean mass (TLM) were measured. Bilateral VL muscle biopsies were collected on Day 4 at t = -120, 0, 90, and 180 min to determine integrated MPS, estimated MPB, acute fasted-fed MPS (l-[ring-13 C6 ]-phe), and acute fasted tracer decay rate representative of MPB (l-[15 N]-phe and l-[2 H8 ]-phe). Protein turnover cell signalling was measured by immunoblotting. RESULTS: Immobilization decreased TLM [pre 7477 ± 1196 g, post 7352 ± 1209 g (P < 0.01)], MT [pre 2.67 ± 0.50 cm, post 2.55 ± 0.51 cm (P < 0.05)], and strength [pre 260 ± 43 N m, post 229 ± 37 N m (P < 0.05)] with no change in control legs. Integrated MPS decreased in immob vs. control legs [control 1.55 ± 0.21% day-1 , immob 1.29 ± 0.17% day-1 (P < 0.01)], while tracer decay rate (i.e. MPB) (control 0.02 ± 0.006, immob 0.015 ± 0.015) and fractional breakdown rate (FBR) remained unchanged [control 1.44 ± 0.51% day-1 , immob 1.73 ± 0.35% day-1 (P = 0.21)]. Changes in MT correlated with those in MPS but not FBR. MPS increased in the control leg following feeding [fasted 0.043 ± 0.012% h-1 , fed 0.065 ± 0.017% h-1 (P < 0.05)] but not in immob [fasted 0.034 ± 0.014% h-1 , fed 0.049 ± 0.023% h-1 (P = 0.09)]. There were no changes in markers of MPB with immob (P > 0.05). CONCLUSIONS: Human skeletal muscle disuse atrophy is driven by declines in MPS, not increases in MPB. Pro-anabolic therapies to mitigate disuse atrophy would likely be more effective than therapies aimed at attenuating protein degradation.