亮氨酸及其在癌症恶病质诱导的肌肉萎缩细胞信号通路中的重要性

André Gustavo Oliveira, B. Cruz, Sarah Christine Pereira de Oliveira, L. Viana, Natália Angelo da Silva Miyaguti, L. Ramos, Rafael R Valentim, M. Gomes-Marcondes
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引用次数: 0

摘要

在膳食中添加支链氨基酸,特别是亮氨酸,对骨骼肌萎缩的合成代谢作用,以及作为癌症治疗的辅助剂,已经得到了很好的研究。亮氨酸是蛋白质合成的前体,作为营养信号,影响多种代谢过程(如饱腹感、产热、能量效率和身体成分)。先前与营养治疗相关的研究主要集中在肌萎缩症上,即在包括癌症在内的某些病理中骨骼肌质量的减少。亮氨酸在维持甚至增加健康个体的瘦体重以及预防最终导致肌萎缩的疾病状态中发挥作用。在此,我们回顾了现有的数据解决机制的亮氨酸作为一个细胞信号,从而刺激肌肉蛋白质合成,导致肌肉分解代谢的抑制,特别是在癌症恶病质的实验模型。我们还展示了代谢组学和蛋白质组学分析中发现的差异,包括在母体饮食中使用亮氨酸作为肌肉萎缩的预防措施,这一点得到了我们实验数据的支持。
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Leucine and Its Importance for Cell Signalling Pathways in Cancer Cachexia-Induced Muscle Wasting
The anabolic effects of a supplemented diet with branched-chain amino acids, especially leucine, on skeletal muscle wasting and as a co-adjuvant in cancer treatment have been well-studied. Leucine is a precursor of protein synthesis and acts as a nutritional signal, affecting multiple metabolic processes (e.g., satiety, thermo-genesis, energy efficiency, and body composition). Previous studies related to nutritional therapy have mainly focused on myopenia, which is the loss of skeletal muscle mass in some pathologies, including cancer. Leucine plays a role in the maintenance and even increase of lean body mass in healthy individuals as well as the prevention of disease states that culminate in myopenia. Herein, we review the available data addressing the mechanisms by which leucine acts as a cellular signal, thereby stimulating muscle protein synthesis, leading to the inhibition of muscle catabolism, especially in an experimental model of cancer cachexia. We also show differences found in the metabolomic and proteomic analyses, including the use of leucine in maternal diets as a preventative for muscle wasting as supported by our experimental data.
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