van Norren Klaske, Dwarkasing Jvalini T, Witkamp Renger F
aDivision of Human Nutrition, Nutrition and Pharmacology Group, Wageningen University, Wageningen bNutricia Research, Utrecht, the Netherlands.
Curr Opin Clin Nutr Metab Care. 2017 Sep;20(5):396-401. doi: 10.1097/MCO.0000000000000401.
In cancer patients, the development of cachexia (muscle wasting) is frequently aggravated by anorexia (loss of appetite). Their concurrence is often referred to as anorexia-cachexia syndrome. This review focusses on the recent evidence underlining hypothalamic inflammation as key driver of these processes. Special attention is given to the involvement of hypothalamic serotonin.
The anorexia-cachexia syndrome is directly associated with higher mortality in cancer patients. Recent reports confirm its severe impact on the quality of life of patients and their families.Hypothalamic inflammation has been shown to contribute to muscle and adipose tissue loss in cancer via central hypothalamic interleukine (IL)1β-induced activation of the hypothalamic-pituitary-adrenal axis. The resulting release of glucocorticoids directly stimulates catabolic processes in these tissues via activation of the ubiquitin-proteosome pathway. Next to this, hypothalamic inflammation has been shown to reduce food intake in cancer by triggering changes in orexigenic and anorexigenic responses via upregulation of serotonin availability and stimulation of its signalling pathways in hypothalamic tissues. This combination of reduced food intake and stimulation of tissue catabolism represents a dual mechanism by which hypothalamic inflammation contributes to the development and maintenance of anorexia and cachexia in cancer.
Hypothalamic inflammation is a driving force in the development of the anorexia-cachexia syndrome via hypothalamic-pituitary-adrenal axis and serotonin pathway activation.
在癌症患者中，恶病质（肌肉消耗）的发展常因厌食（食欲不振）而加剧。它们同时出现常被称为厌食 - 恶病质综合征。本综述聚焦于强调下丘脑炎症是这些过程关键驱动因素的最新证据。特别关注下丘脑5-羟色胺的作用。
厌食 - 恶病质综合征与癌症患者较高的死亡率直接相关。最近的报告证实了其对患者及其家庭生活质量的严重影响。下丘脑炎症已被证明通过下丘脑白细胞介素（IL）-1β诱导的下丘脑 - 垂体 - 肾上腺轴激活，导致癌症患者肌肉和脂肪组织流失。由此产生的糖皮质激素释放通过激活泛素 - 蛋白酶体途径直接刺激这些组织中的分解代谢过程。除此之外，下丘脑炎症已被证明通过上调5-羟色胺可用性并刺激其在下丘脑组织中的信号通路，引发食欲调节和厌食反应的变化，从而减少癌症患者的食物摄入量。食物摄入量减少和组织分解代谢刺激的这种组合代表了一种双重机制，通过该机制下丘脑炎症促进了癌症患者厌食和恶病质的发展和维持。
下丘脑炎症通过下丘脑 - 垂体 - 肾上腺轴和5-羟色胺途径激活，是厌食 - 恶病质综合征发展的驱动力。
