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

141 Citations (Scopus)

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

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Muscle Proteins
Bed Rest
Atrophy
Leg
Muscle
Hydrocortisone
Healthy Volunteers
Kinetics
Wounds and Injuries
Muscle Strength
Succinic Acid
Body Composition
Phenylalanine
Volunteers
Sodium
Outcome Assessment (Health Care)
Plasmas
Muscles
Chemical analysis
Research

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

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

Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress. / Paddon-Jones, Douglas; Sheffield-Moore, Melinda; Cree, Melanie G.; Hewlings, Susan J.; Aarsland, Asle; Wolfe, Robert R.; Ferrando, Arny A.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 91, No. 12, 12.2006, p. 4836-4841.

Research output: Contribution to journalArticle

Paddon-Jones, D, Sheffield-Moore, M, Cree, MG, Hewlings, SJ, Aarsland, A, Wolfe, RR & Ferrando, AA 2006, 'Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress', Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 12, pp. 4836-4841. https://doi.org/10.1210/jc.2006-0651
Paddon-Jones, Douglas ; Sheffield-Moore, Melinda ; Cree, Melanie G. ; Hewlings, Susan J. ; Aarsland, Asle ; Wolfe, Robert R. ; Ferrando, Arny A. / Atrophy and impaired muscle protein synthesis during prolonged inactivity and stress. In: Journal of Clinical Endocrinology and Metabolism. 2006 ; Vol. 91, No. 12. pp. 4836-4841.
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