Atrophy and Impaired Muscle Protein Synthesis During Prolonged Inactivity and Stress

J Clin Endocrinol Metab. 2006 Dec;91(12):4836-41. doi: 10.1210/jc.2006-0651. Epub 2006 Sep 19.

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.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Bed Rest / adverse effects*
  • Body Composition
  • Humans
  • Hydrocortisone / administration & dosage
  • Hydrocortisone / adverse effects
  • Hydrocortisone / blood
  • Insulin / blood
  • Male
  • 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
  • Stress, Physiological / complications
  • Stress, Physiological / metabolism*

Substances

  • Insulin
  • Muscle Proteins
  • Phenylalanine
  • Hydrocortisone