Ham Daniel J, Caldow Marissa K, Chhen Victoria, Chee Annabel, Wang Xuemin, Proud Christopher G, Lynch Gordon S, Koopman René
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.
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.
氨基酸，尤其是亮氨酸，能有效刺激健康骨骼肌中的蛋白质合成并减少蛋白质分解，因此作为肌肉萎缩的潜在治疗方法受到了广泛关注。然而，在肌肉萎缩状态下，对氨基酸的正常合成代谢反应会受损。尽管这种合成代谢抵抗的确切机制尚不清楚，但炎症和活性氧被认为起着核心作用。非必需氨基酸甘氨酸具有抗炎和抗氧化特性，并能在热量限制和荷瘤小鼠中维持肌肉质量。我们假设甘氨酸能在炎症条件下恢复肌肉对氨基酸的正常合成代谢反应。在注射1mg/kg脂多糖（LPS）4小时后，使用SUnSET方法测量基础和亮氨酸刺激的蛋白质合成相对速率。在用L-丙氨酸（等氮对照）预处理的LPS处理小鼠中，亮氨酸未能刺激肌肉蛋白质合成，而在用1g/kg甘氨酸预处理的小鼠中，亮氨酸强烈刺激蛋白质合成（增加51%）。与L-丙氨酸处理的对照组相比，亮氨酸刺激的蛋白质合成改善伴随着mTOR、S6和4E-BP1的磷酸化状态更高。尽管甘氨酸在炎症细胞中具有已知的抗炎作用，但它在体内或体外均未改变骨骼肌对LPS的炎症反应，但显著降低了肌肉横切面上氧化应激标志物DHE染色强度，并减轻了LPS诱导的C2C12肌管萎缩。我们在雄性C57BL/6小鼠中的观察结果表明，甘氨酸可能是一种有前景的营养干预措施，可减轻骨骼肌萎缩。
