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

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-C-13(6)]-phe), and acute fasted tracer decay rate representative of MPB (l-[N-15]-phe and l-[H-2(8)]-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.