Cited by 254Muscle metabolism and nutritionSpaceflight effects on biologyMuscle Physiology and Disorders

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.·2006·The Journal of Clinical Endocrinology & Metabolism

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 micromol/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 (approximately 22 microg/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.

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Crossref · 10.1210/jc.2006-0651

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  • A sample size of 13 was calculated to minimize the risk of type II error for the primary outcome FSR (β = 0.2, α = 0.05).

    “Using data from studies investigating the effects of an anabolic and catabolic stimulus (e.g., immobilization or exercise) on changes in muscle protein synthesis (Lamon et al., 2016; Paddon‐Jones et al., 2006), power analyses conducted on our primary outcome (FSR) indicated that a sample size of 13 would minimize the risk of type II error (β = 0.2,α = 0.05).”
  • Muscle loss during bed rest appears to be driven primarily by a reduction in muscle protein synthesis.

    “Muscle loss during bed rest appears to be driven primarily by a reduction in muscle protein synthesis [13-15].”
  • Pharmacologically induced hypercortisolemia (approximately 22 μg/dl) and 28 days of bed rest in young adults resulted in a 3-fold greater loss of leg lean mass than eucortisolemic controls (-1.3 kg vs. -0.4 kg).

    “For example, recent work has demonstrated that the concomitant effects of pharmacologically induced hypercortisolemia (i.e., approx. 22 μg · dl-1) and 28 day of bed rest in young adults, resulted in a 3-fold greater loss of leg lean mass than eucortisolemic controls (-1.3 kg vs. -0.4 kg) [14].”

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Authors
Paddon-Jones, D., Sheffield-Moore, M., Cree, M. G., Hewlings, S. J., Aarsland, A., Wolfe, R. R., & Ferrando, A. A.
Affiliations
  • Departments of Surgery (D.P.-J., M.G.C., S.J.H., A.A., R.R.W., A.A.F.), Galveston, Texas 77550
  • Internal Medicine (M.S.-M.) Galveston, Texas 77550
  • The University of Texas Medical Branch at Galveston (US)
Venue
The Journal of Clinical Endocrinology & Metabolism
Published
2006-12-01
Volume
91
Issue
12
Pages
4836-4841
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
OpenAlex
W2033713750
Cited by
254
References
40
Citations by year
2026: 3 · 2025: 3 · 2024: 17 · 2023: 16 · 2022: 15 · 2021: 17 · 2020: 16 · 2019: 13 · 2018: 7 · 2017: 7 · 2016: 14 · 2015: 16 · 2014: 15 · 2013: 21 · 2012: 15
FWCI
3.86
Type
journal article
Language
en
Open access
closed
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Aeronautics and Space Administration (NAG91155)
  • University of Texas Medical Branch
  • Deutsches Krebsforschungszentrum
  • Shriners Hospitals for Children
  • National Institutes of Health
  • National Institute on Aging (P30AG024832)
  • National Institute of General Medical Sciences (5R01 GM 57295, R01GM057295)
  • National Center for Research Resources (M01 RR-00073, M01RR000073)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Physiology › Spaceflight effects on biology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
muscle atrophy, muscle protein synthesis, muscle protein degradation, bed rest, physical inactivity, hypercortisolism, cortisol, stress response, lean muscle mass, leg extension strength, body composition
MeSH terms
Adult, Bed Rest, Body Composition, Humans, Hydrocortisone, Insulin, Male, Motor Activity, Muscle Proteins, Muscular Atrophy, Phenylalanine, Stress, Physiological, Muscle, Skeletal

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