Hypothalamus metabolomic profiling to elucidate the tissue-targeted biochemical basis of febrile response in yeast-induced pyrexia rats
Hypothalamus metabolomic profiling to elucidate the tissue-targeted biochemical basis of febrile response in yeast-induced pyrexia rats
复制标题
下丘脑代谢组学分析阐明酵母引起的发热大鼠发热反应的组织靶向生化基础
DOI：
10.1016/j.cbi.2015.02.018
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发表时间：
2015-04-25
影响因子：
5.1
通讯作者：
Gao, Xiaoyan
中科院分区：
文献类型：
--
作者：
Liu, Haiyu;Zhang, Li;Gao, Xiaoyan
在先前关于体温调节的报道中，下丘脑被认为是中枢神经系统中控制体温的主要中心。然而，迄今为止，还没有足够的证据来揭示其体温调节机制。在目前的研究中，我们利用组织靶向代谢组学策略，通过分析酵母诱导的发热大鼠下丘脑的整体代谢谱来阐明发热过程中体温调节的潜在生化机制。使用HPLC-LTQ-Orbitrap/MS在正离子和负离子模式下完成数据采集。采用主成分分析法观察发热组与对照组之间的聚类特征。使用正交偏最小二乘判别分析筛选潜在的生物标志物。在下丘脑样本中鉴定了17种潜在的生物标志物，以区分对照组和发热组，包括氨基酸、核酸、维生素、碳水化合物和磷脂。结果，嘌呤代谢明显增强，脂质代谢也受到干扰。同时，氨基酸代谢和能量代谢也被显著激活。本研究表明，下丘脑靶向代谢组学可以为进一步了解发热反应的发病机制提供有力的工具。(C)2015爱思唯尔爱尔兰有限公司版权所有。
In the previous reports regarding thermoregulation, the hypothalamus is thought to be the primary centre in the central nervous system for controlling the body temperature. However, to date, there has not been sufficient evidence to reveal its thermoregulatory mechanism. In the current study, we utilised a tissue-targeted metabolomics strategy to elucidate the underlying biochemical mechanisms of thermoregulation in the fever process by analysing the global metabolic profile of the hypothalamus in yeast-induced pyrexia rats. Data acquisition was completed using the HPLC-LTQ-Orbitrap/MS in both positive and negative ion mode. Principal component analysis was used to observe the cluster characteristics between the control group and the pyrexia group. Potential biomarkers were screened using orthogonal partial least-squares-discriminant analysis. Seventeen potential biomarkers were identified in the hypothalamus samples to discriminate the control and pyrexia groups, including amino acids, nucleic acids, vitamins, carbohydrates, and phospholipids. As a result, purine metabolism was enhanced pronouncedly, and perturbation of lipid metabolism was also observed. Meanwhile, amino acid metabolism and energy metabolism were also activated significantly. In conclusion, the study indicated that hypothalamus-targeted metabolomics could provide a powerful tool to further understand the pathogenesis of febrile response. (C) 2015 Elsevier Ireland Ltd. All rights reserved.