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

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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

DOI 10.1210/jc.2006-0651

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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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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)
ORCID: Hewlings, Susan J.
Wolfe, Robert R.
Ferrando, Arny A.
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2006-12-01
Volume: 91
Issue: 12
Pages: 4836-4841
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2006-0651
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: Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
Health Sciences › Medicine › Physiology (medical) › 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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Atrophy and Impaired Muscle Protein Synthesis during Prolonged Inactivity and Stress

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