Potential biomarkers of fatigue identified by plasma metabolome analysis in rats.
Potential biomarkers of fatigue identified by plasma metabolome analysis in rats.
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DOI：
10.1371/journal.pone.0120106
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Kataoka Y
中科院分区：
文献类型：
--
作者：
Kume S;Yamato M;Tamura Y;Jin G;Nakano M;Miyashige Y;Eguchi A;Ogata Y;Goda N;Iwai K;Yamano E;Watanabe Y;Soga T;Kataoka Y
在本研究中，在建立人类慢性疲劳临床诊断方法之前，我们使用毛细管电泳-质谱法（CE-MS）验证了血浆代谢组学分析在大鼠疲劳模型中的实用性。为了获得疲劳的动物组，将大鼠放入装满水至2.2cm高度的笼子中5天。还对食物限制组进行了评估，其中大鼠每天的食物限制为 10 克（约为对照组的 50%）。限制食物组的体重减轻与疲劳组相似。进行 CE-MS 测量以评估食物摄入依赖性代谢变化的概况以及疲劳负荷的概况，从而鉴定出血浆中的 48 种代谢物。使用层次聚类和主成分分析的多变量分析表明，疲劳组的血浆代谢组与对照组和食物限制组有明显差异。在疲劳组中，我们发现与支链氨基酸代谢、尿素循环和脯氨酸代谢相关的代谢物发生了明显的变化。具体来说，与对照组和食物限制组相比，疲劳组的缬氨酸、亮氨酸、异亮氨酸和2-氧代异戊酸显着增加，瓜氨酸和羟脯氨酸显着减少。疲劳组的血浆总一氧化氮水平升高，表明全身氧化应激。此外，疲劳组中参与柠檬酸循环的血浆代谢物（例如顺乌头酸和异柠檬酸）减少。肝脏和骨骼肌中的 ATP 水平显着下降，表明这些器官的能量代谢恶化。因此，这种全面的代谢分析加深了我们对疲劳病理生理学的理解，并根据疲劳病理生理学确定了潜在的诊断生物标志物。
In the present study, prior to the establishment of a method for the clinical diagnosis of chronic fatigue in humans, we validated the utility of plasma metabolomic analysis in a rat model of fatigue using capillary electrophoresis-mass spectrometry (CE-MS). In order to obtain a fatigued animal group, rats were placed in a cage filled with water to a height of 2.2 cm for 5 days. A food-restricted group, in which rats were limited to 10 g/d of food (around 50% of the control group), was also assessed. The food-restricted group exhibited weight reduction similar to that of the fatigued group. CE-MS measurements were performed to evaluate the profile of food intake-dependent metabolic changes, as well as the profile in fatigue loading, resulting in the identification of 48 metabolites in plasma. Multivariate analyses using hierarchical clustering and principal component analysis revealed that the plasma metabolome in the fatigued group showed clear differences from those in the control and food-restricted groups. In the fatigued group, we found distinctive changes in metabolites related to branched-chain amino acid metabolism, urea cycle, and proline metabolism. Specifically, the fatigued group exhibited significant increases in valine, leucine, isoleucine, and 2-oxoisopentanoate, and significant decreases in citrulline and hydroxyproline compared with the control and food-restricted groups. Plasma levels of total nitric oxide were increased in the fatigued group, indicating systemic oxidative stress. Further, plasma metabolites involved in the citrate cycle, such as cis-aconitate and isocitrate, were reduced in the fatigued group. The levels of ATP were significantly decreased in the liver and skeletal muscle, indicative of a deterioration in energy metabolism in these organs. Thus, this comprehensive metabolic analysis furthered our understanding of the pathophysiology of fatigue, and identified potential diagnostic biomarkers based on fatigue pathophysiology.
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影响因子：
56.9
作者：
Ishii, Nobuyoshi;Nakahigashi, Kenji;Tomita, Masaru
通讯作者：
Tomita, Masaru
影响因子：
7.4
作者：
Soga, T;Heiger, DN
通讯作者：
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DOI：
10.1155/2012/109636
发表时间：
2012
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
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通讯作者：
Mohd Yusof YA
影响因子：
4.7
作者：
Ogawa, Tokiko;Shishioh-Ikejima, Nobue;Kiyama, Hiroshi
通讯作者：
Kiyama, Hiroshi
影响因子：
2.5
作者：
LEHMANN, M;HUONKER, M;HAUSSINGER, D
通讯作者：
HAUSSINGER, D