Background:Disuse leads to rapid skeletal muscle atrophy which brings about numerous negative health consequences. Muscle disuse atrophy is, at least in part, attributed to a decline in basal (post-absorptive) muscle protein synthesis rates. However, it remains to be determined whether muscle disuse also impairs the muscle protein synthetic response to dietary protein ingestion.Purpose:We assessed muscle protein synthesis rates following protein ingestion before and after a period of disuse in humans.Methods:Twelve healthy, young (24+/-1 y) men underwent a 14 day period of one-legged knee immobilization by way of a full leg cast. Before and after the immobilization period, quadriceps cross sectional area (CSA), muscle strength, skeletal muscle protein synthesis rates, and associated intramuscular molecular signaling were assessed. Continuous infusions of L-[ring-2H5]phenylalanine were applied to assess mixed muscle protein fractional synthetic rates (FSRs) following the ingestion of 20 g dietary protein.Results:Immobilization led to an 8.4+/-2.8 (P<0.001) and 22.9+/-2.6% (P<0.001) decrease in quadriceps muscle CSA and strength, respectively. Immobilization resulted in a 31+/-12% reduction in post-prandial muscle protein synthesis rates (from 0.046+/-0.004 to 0.032+/-0.006 %.h-1; P<0.05). These findings were observed without any discernible changes in the skeletal muscle phosphorylation status of mammalian target of rapamycin (mTOR) or p70 ribosomal protein S6 kinase (p70S6K).Conclusions:A short period of muscle disuse impairs the muscle protein synthetic response to dietary protein intake in vivo in healthy young men. Thus, anabolic resistance to protein ingestion contributes significantly to the loss of muscle mass that is observed during disuse.