Short-term muscle disuse lowers myofibrillar protein synthesis rates and induces anabolic resistance to protein ingestion

Disuse leads to rapid loss of skeletal muscle mass and function. It has been hypothesized that short, successive periods of muscle disuse throughout the lifespan play an important role in the development of sarcopenia. The physiological mechanisms underlying short-term muscle disuse atrophy remain to be elucidated. We assessed the impact of five days of muscle disuse on post-absorptive and post-prandial myofibrillar protein synthesis rates in humans. Twelve healthy, young (22+/-1 y) men underwent a five day period of one-legged knee immobilization (full leg cast). Quadriceps cross-sectional area (CSA) of both legs was assessed before and after immobilization. Continuous infusions of L-[ring-2H5]phenylalanine and L-[1-13C]leucine were combined with the ingestion of a 25 g bolus of intrinsically L-[1-13C]phenylalanine and L-[1-13C]leucine labelled dietary protein to assess myofibrillar muscle protein fractional synthetic rates (FSRs) in the immobilized and non-immobilized control leg. Immobilization led to a 3.9+/-0.6 % decrease in quadriceps muscle CSA of the immobilized leg. Based on the L-[ring-2H5]phenylalanine tracer, immobilization reduced post-absorptive myofibrillar protein synthesis rates by 41+/-13% (0.015+/-0.002 vs 0.032+/-0.005 %.h-1; P<0.01) and post-prandial myofibrillar protein synthesis rates by 53+/-4% (0.020+/-0.002 vs 0.044+/-0.003 %.h-1; P<0.01). Comparable results were found using the L-[1-13C]leucine tracer. Following protein ingestion, myofibrillar protein bound L-[1-13C]phenylalanine enrichments were 53+/-18% lower in the immobilized compared with the control leg (0.007+/-0.002 and 0.015+/-0.002 MPE, respectively; P<0.05). We conclude that five days of muscle disuse substantially lowers post-absorptive myofibrillar protein synthesis rates and induces anabolic resistance to protein ingestion.