Glycine restores the anabolic response to leucine in a mouse model of acute inflammation.
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.
Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia;
Daniel J
DJ
Ham
Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia;
Marissa K
MK
Caldow
Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia;
Victoria
V
Chhen
Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia;
Annabel
A
Chee
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.
Xuemin
X
Wang
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.
Christopher G
CG
Proud
Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia;
Gordon S
GS
Lynch
Basic and Clinical Myology Laboratory, Department of Physiology, University of Melbourne, Melbourne, Victoria, Australia; rkoopman@unimelb.edu.au.
René
R
Koopman
D000208:Acute Disease; D045930:Anabolic Agents / Q000008:administration & dosage; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D004357:Drug Synergism; D005998:Glycine / Q000008:administration & dosage*; D007930:Leucine / Q000008:administration & dosage*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009124:Muscle Proteins / Q000096:biosynthesis; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D009220:Myositis / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
D045930:Anabolic Agents; D008070:Lipopolysaccharides; D009124:Muscle Proteins; D007930:Leucine; D005998:Glycine
Protein synthesis; atrophy; muscle wasting; sepsis