Atrophy and Impaired Muscle Protein Synthesis during Prolonged Inactivity and Stress

• Published in: The journal of clinical endocrinology and metabolism Vol. 91; no. 12; pp. 4836 - 4841
• Main Authors: Paddon-Jones, Douglas, Sheffield-Moore, Melinda, Cree, Melanie G., Hewlings, Susan J., Aarsland, Asle, Wolfe, Robert R., Ferrando, Arny A.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Oxford University Press 01.12.2006; Endocrine Society
• Subjects: Adult; Atrophy; Bed Rest - adverse effects; Biological and medical sciences; Body Composition; Endocrinopathies; Fundamental and applied biological sciences. Psychology; Humans; Hydrocortisone; Hydrocortisone - administration & dosage; Hydrocortisone - adverse effects; Hydrocortisone - blood; Immobilization; Insulin - blood; Leg; Male; Medical sciences; Motor Activity - physiology; Muscle Proteins - biosynthesis; Muscle, Skeletal - drug effects; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Muscular Atrophy - etiology; Muscular Atrophy - metabolism; Muscular Atrophy - pathology; Phenylalanine - blood; Protein biosynthesis; Protein composition; Protein folding; Protein synthesis; Proteins; Sodium succinate; Stress, Physiological - complications; Stress, Physiological - metabolism; Vertebrates: endocrinology; Atrophy; Muscle; Protein synthesis; Endocrinology; Stress; Prolonged
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2006-0651

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.