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

Abstract

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‐13C6]‐phe), and acute fasted tracer decay rate representative of MPB (l‐[15N]‐phe and l‐[2H8]‐phe). Protein turnover cell signalling was measured by immunoblotting. Results Immobilization decreased TLM [pre: 7477 ± 1196 g, post: 7352 ± 1209 g (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.

Keywords

• Immobilization
• Atrophy
• Muscle
• Protein synthesis
• Protein breakdown