Inflammatory burden and amino acid metabolism in cancer cachexia.
Inflammatory burden and amino acid metabolism in cancer cachexia.
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DOI：
10.1097/mco.0b013e32831cef61
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发表时间：
2009-01
影响因子：
3.1
通讯作者：
Sheffield-Moore M
中科院分区：
文献类型：
--
作者：
Durham WJ;Dillon EL;Sheffield-Moore M
癌症恶病质与骨骼肌蛋白质代谢的显着改变有关，导致肌肉萎缩，在某些情况下甚至导致死亡。癌症引起的炎症反应即使不是主要的，也可能是这些改变的中介因素。本综述重点关注癌症中炎症信号传导与氨基酸代谢改变之间的可能关系。癌症患者骨骼肌的损失可能是由于厌食和早饱、肌肉蛋白质合成减少和/或肌肉蛋白质分解增加所致。炎症与这些机制中的每一种都相关。对食欲的影响似乎是由下丘脑的黑皮质素系统介导的。对恶病质动物模型的研究表明，调节该系统中的食欲和厌食途径可能会改善营养消耗。 IL-6 和 TNFα 等炎症细胞因子可能通过多种途径影响炎症对肌肉蛋白代谢的影响。对人类的有限研究表明，有针对性的抗炎和营养干预可能会改善对骨骼肌蛋白质代谢的净分解代谢效应。未来有必要研究肌肉蛋白质损失的精确机制，以及抑制炎症和促进合成代谢的新颖或联合疗法。
Cancer cachexia is associated with marked alterations in skeletal muscle protein metabolism that lead to muscle wasting and, in some cases, death. The inflammatory response elicited by cancer is a likely, if not primary, mediator of these alterations. This review focuses on the possible relationship between inflammatory signaling and altered amino acid metabolism in cancer. Loss of skeletal muscle in cancer patients can potentially be due to anorexia and early satiety, reduced muscle protein synthesis, and/or increased muscle protein breakdown. Inflammation has been associated with each of these mechanisms. Effects on appetite appear to be mediated by the melanocortin system in the hypothalamus. Studies in animal models of cachexia suggest that modulation of orexigenic and anorexigenic pathways in this system may improve nutrient consumption. Inflammatory cytokines such as IL-6 and TNFα likely contribute to the effects of inflammation on muscle protein metabolism through several pathways. Limited studies in humans suggest that targeted anti-inflammatory and nutritional interventions may ameliorate the net catabolic effect on skeletal muscle protein metabolism. Future studies of the precise mechanism of muscle protein loss, as well as novel or combination therapies to inhibit inflammation and promote anabolism, are warranted.