Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress

Douglas Paddon-Jones, Melinda Sheffield-Moore, Melanie G. Cree, Susan J. Hewlings, Asle Aarsland, Robert R. Wolfe, Arny A. Ferrando

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

Context: We recently demonstrated that 28-d bed rest in healthy volunteers results in a moderate loss of lean leg mass and strength. Objective: The objective of this study was to quantify changes in muscle protein kinetics, body composition, and strength during a clinical bed rest model reflecting both physical inactivity and the hormonal stress response to injury or illness. Design: Muscle protein kinetics were calculated during a primed, continuous infusion (0.08 μmol/kg·min) of 13C6- phenylalanine on d 1 and 28 of bed rest. Setting: The setting for this study was the General Clinical Research Center at the University of Texas Medical Branch. Participants: Participants were healthy male volunteers (n = 6, 28 ± 2 yr, 84 ± 4 kg, 178 ± 3 cm). Intervention: During bed rest, hydrocortisone sodium succinate was administered iv (d 1 and 28) and orally (d 2-27) to reproduce plasma cortisol concentrations consistent with trauma or illness (∼22 μg/dl). Main Outcome Measures: We hypothesized that inactivity and hypercortisolemia would reduce lean muscle mass, leg extension strength, and muscle protein synthesis. Results: Volunteers experienced a 28.4 ± 4.4% loss of leg extension strength (P = 0.012) and a 3-fold greater loss of lean leg mass (1.4 ± 0.1 kg) (P = 0.004) compared with our previous bed rest-only model. Net protein catabolism was primarily due to a reduction in muscle protein synthesis [fractional synthesis rate, 0.081 ± 0.004 (d 1) vs. 0.054 ± 0.007%/h (d 28); P = 0.023]. There was no change in muscle protein breakdown. Conclusion: Prolonged inactivity and hypercortisolemia represents a persistent catabolic stimulus that exacerbates strength and lean muscle loss via a chronic reduction in muscle protein synthesis.

Original languageEnglish (US)
Pages (from-to)4836-4841
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Volume91
Issue number12
DOIs
StatePublished - Dec 2006

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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    Paddon-Jones, D., Sheffield-Moore, M., Cree, M. G., Hewlings, S. J., Aarsland, A., Wolfe, R. R., & Ferrando, A. A. (2006). Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress. Journal of Clinical Endocrinology and Metabolism, 91(12), 4836-4841. https://doi.org/10.1210/jc.2006-0651