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

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

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Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia;
Nutrition and Metabolism, South Australian Health and Medical Research Institute, Adelaide, South Austrailia, Australia; and School of Biological Sciences, University of Adelaide, Adelaide, South Australia, Australia.
Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia;


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.


Protein synthesis; atrophy; muscle wasting; sepsis

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