Glycine restores the anabolic response to leucine in a mouse model of acute inflammation

Daniel J. Ham, Marissa K. Caldow, Victoria Chhen, Annabel Chee, Xuemin Wang, Christopher G. Proud, Gordon S. Lynch, René Koopman

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Amino acids, especially leucine, potently stimulate protein synthesis and reduce protein breakdown in healthy skeletal muscle and as a result have received considerable attention as potential treatments for muscle wasting. However, the normal anabolic response to amino acids is impaired during muscle-wasting conditions. Although the exact mechanisms of this anabolic resistance are unclear, inflammation and ROS are believed to play a central role. The nonessential amino acid glycine has anti-inflammatory and antioxidant properties and preserves muscle mass in calorie-restricted and tumor-bearing mice. We hypothesized that glycine would restore the normal muscle anabolic response to amino acids under inflammatory conditions. Relative rates of basal and leucine-stimulated protein synthesis were measured using SUnSET methodology 4 h after an injection of 1 mg/kg lipopolysaccharide (LPS). Whereas leucine failed to stimulate muscle protein synthesis in LPS-treated mice pretreated with L-alanine (isonitrogenous control), leucine robustly stimulated protein synthesis (+51%) in mice pretreated with 1 g/kg glycine. The improvement in leucinestimulated protein synthesis was accompanied by a higher phosphorylation status of mTOR, S6, and 4E-BP1 compared with L-alaninetreated controls. Despite its known anti-inflammatory action in inflammatory cells, glycine did not alter the skeletal muscle inflammatory response to LPS in vivo or in vitro but markedly reduced DHE staining intensity, a marker of oxidative stress, in muscle cross-sections and attenuated LPS-induced wasting in C2C12 myotubes. Our observations in male C57BL/6 mice suggest that glycine may represent a promising nutritional intervention for the attenuation of skeletal muscle wasting.

LanguageEnglish
PagesE970-E981
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume310
Issue number11
DOIs
Publication statusPublished - 1 Jun 2016

Keywords

  • Atrophy
  • Muscle wasting
  • Protein synthesis
  • Sepsis

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

Ham, Daniel J. ; Caldow, Marissa K. ; Chhen, Victoria ; Chee, Annabel ; Wang, Xuemin ; Proud, Christopher G. ; Lynch, Gordon S. ; Koopman, René. / Glycine restores the anabolic response to leucine in a mouse model of acute inflammation. In: American Journal of Physiology - Endocrinology and Metabolism. 2016 ; Vol. 310, No. 11. pp. E970-E981.
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Glycine restores the anabolic response to leucine in a mouse model of acute inflammation. / Ham, Daniel J.; Caldow, Marissa K.; Chhen, Victoria; Chee, Annabel; Wang, Xuemin; Proud, Christopher G.; Lynch, Gordon S.; Koopman, René.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 310, No. 11, 01.06.2016, p. E970-E981.

Research output: Contribution to journalArticle

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T1 - Glycine restores the anabolic response to leucine in a mouse model of acute inflammation

AU - Ham, Daniel J.

AU - Caldow, Marissa K.

AU - Chhen, Victoria

AU - Chee, Annabel

AU - Wang, Xuemin

AU - Proud, Christopher G.

AU - Lynch, Gordon S.

AU - Koopman, René

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KW - Protein synthesis

KW - Sepsis

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