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

Am J Physiol Endocrinol Metab. 2016 Jun 1;310(11):E970-81. doi: 10.1152/ajpendo.00468.2015. Epub 2016 Apr 19.


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 leucine-stimulated protein synthesis was accompanied by a higher phosphorylation status of mTOR, S6, and 4E-BP1 compared with l-alanine-treated 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.

Keywords: Protein synthesis; atrophy; muscle wasting; sepsis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Anabolic Agents / administration & dosage
  • Animals
  • Dose-Response Relationship, Drug
  • Drug Resistance
  • Drug Synergism
  • Glycine / administration & dosage*
  • Leucine / administration & dosage*
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle Proteins / biosynthesis
  • Muscular Atrophy / drug therapy*
  • Muscular Atrophy / metabolism*
  • Muscular Atrophy / pathology
  • Myositis / drug therapy*
  • Myositis / metabolism*
  • Myositis / pathology
  • Treatment Outcome


  • Anabolic Agents
  • Lipopolysaccharides
  • Muscle Proteins
  • Leucine
  • Glycine