Basic and Clinical Myology Laboratory, Department of Physiology, The University of Melbourne, Victoria 3010, Australia.
Clin Nutr. 2014 Dec;33(6):937-45. doi: 10.1016/j.clnu.2014.09.016.
Amino acids are potent modulators of protein turnover and skeletal muscle cells are highly sensitive to changes in amino acid availability. During amino acid abundance increased activity of mTORC1 drives protein synthesis and growth. In skeletal muscle, it has been clearly demonstrated that of all the amino acids, leucine is the most potent stimulator of mTORC1 and protein synthesis in vitro and in vivo. As such, leucine has received considerable attention as a potential pharmaconutrient for the treatment of numerous muscle wasting conditions. However, despite a multitude of studies showing enhanced acute protein synthesis with leucine or leucine-rich supplements in healthy individuals, additional leucine intake does not necessarily enhance protein synthesis during muscle wasting conditions. In addition, long-term, placebo controlled, iso-caloric studies in humans consistently show no beneficial effect of leucine supplementation on skeletal muscle mass or function. This review, critically evaluates the therapeutic potential of leucine to attenuate the skeletal muscle wasting associated with ageing, cancer and immobilization/bed rest. It also highlights the impact of inflammation on amino acid sensing, mTORC1 activation and stimulation of protein synthesis and challenges the underlying hypothesis that the acute activation of mTORC1 and stimulation of protein synthesis by leucine increases in muscle mass over time. We conclude that leucine, as a standalone nutritional intervention, is not effective in the prevention of muscle wasting. Future work should focus on identifying and utilizing other nutrients or treatments that sensitize skeletal muscle to leucine, thereby enhancing its therapeutic potential for muscle wasting conditions.
氨基酸是蛋白质周转率的有效调节剂，骨骼肌肉细胞对氨基酸可用性的变化高度敏感。在氨基酸丰富的情况下，mTORC1 的活性增加会促进蛋白质合成和生长。在骨骼肌中，已经清楚地表明，在所有氨基酸中，亮氨酸是体外和体内最能刺激 mTORC1 和蛋白质合成的氨基酸。因此，亮氨酸作为治疗多种肌肉消耗疾病的潜在营养药物受到了相当多的关注。然而，尽管有大量研究表明，在健康个体中，亮氨酸或富含亮氨酸的补充剂可增强急性蛋白质合成，但额外的亮氨酸摄入并不一定能在肌肉消耗情况下增强蛋白质合成。此外，人体的长期、安慰剂对照、等热量研究一致表明，亮氨酸补充对骨骼肌质量或功能没有有益影响。这篇综述批判性地评估了亮氨酸治疗衰老、癌症和固定/卧床相关肌肉消耗的潜力。它还强调了炎症对氨基酸感应、mTORC1 激活和蛋白质合成刺激的影响，并对亮氨酸急性激活 mTORC1 和刺激蛋白质合成会随着时间的推移增加肌肉质量的假设提出了挑战。我们得出结论，亮氨酸作为一种独立的营养干预措施，不能有效预防肌肉消耗。未来的工作应集中于识别和利用其他营养素或治疗方法，使骨骼肌对亮氨酸敏感，从而增强其在肌肉消耗疾病中的治疗潜力。
