Disuse impairs the muscle protein synthetic response to protein ingestion in healthy men

J Clin Endocrinol Metab. 2013 Dec;98(12):4872-81. doi: 10.1210/jc.2013-2098. Epub 2013 Oct 9.

Abstract

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 (postabsorptive) 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 after protein ingestion before and after a period of disuse in humans.

Methods: Twelve healthy young (24 ± 1 year) 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, muscle strength, skeletal muscle protein synthesis rates, and associated im (intramuscular) molecular signaling were assessed. Continuous infusions of l-[ring-²H₅]phenylalanine were applied to assess mixed-muscle protein fractional synthetic rates after the ingestion of 20 g dietary protein.

Results: Immobilization led to an 8.4% ± 2.8% (P < .001) and 22.9% ± 2.6% (P < .001) decrease in quadriceps muscle cross-sectional area and strength, respectively. Immobilization resulted in a 31% ± 12% reduction in postprandial muscle protein synthesis rates (from 0.046% ± 0.004% to 0.032% ± 0.006% per hour; P < .05). These findings were observed without any discernible changes in the skeletal muscle phosphorylation status of mammalian target of rapamycin or p70 ribosomal protein S6 kinase.

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.

MeSH terms

  • Adult
  • Casts, Surgical / adverse effects
  • Deuterium
  • Dietary Proteins / metabolism*
  • Down-Regulation*
  • Humans
  • Kinetics
  • Leg
  • Male
  • Muscle Proteins / biosynthesis*
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Muscle Strength
  • Muscular Atrophy / blood
  • Muscular Atrophy / etiology
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology
  • Phenylalanine / blood
  • Phenylalanine / metabolism
  • Phosphorylation
  • Postprandial Period
  • Protein Processing, Post-Translational
  • Quadriceps Muscle / metabolism
  • Quadriceps Muscle / pathology
  • Restraint, Physical / adverse effects*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism
  • Signal Transduction
  • TOR Serine-Threonine Kinases / metabolism
  • Young Adult

Substances

  • Dietary Proteins
  • Muscle Proteins
  • Phenylalanine
  • Deuterium
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Ribosomal Protein S6 Kinases, 70-kDa