Hara Yurie, Kume Satoshi, Kataoka Yosky, Watanabe Nakamichi
Department of Advanced Food Sciences, College of Agriculture, Tamagawa University, Tokyo, Japan.
Laboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan.
Heliyon. 2021 Dec 4;7(12):e08501. doi: 10.1016/j.heliyon.2021.e08501. eCollection 2021 Dec.
Recent studies have reported that plasma levels of tricarboxylic acid (TCA) cycle metabolites and TCA cycle-related metabolite change in patients with chronic fatigue syndrome (CFS) and in healthy humans after exercise. Exogenous dietary citric acid has been reported to alleviate fatigue during daily activities and after exercise. However, it is unknown whether dietary citric acid affects the plasma levels of these metabolites. Therefore, the present study aimed to investigate the effects of exogenously administered citric acid on TCA cycle metabolites and TCA cycle-related metabolites in plasma. Sprague-Dawley rats were divided into control and citric acid groups. We evaluated the effect of exogenous dietary citric acid on the plasma TCA cycle and TCA cycle-related metabolites by metabolome analysis using liquid chromatography-tandem mass spectrometry (LC-MS/MS). TCA cycle metabolites, including plasma citrate, cis-aconitate, and isocitrate, were significantly elevated after exogenous administration of citric acid. Anaplerotic amino acids, which are converted to TCA cycle metabolites, such as serine, glycine, tryptophan, lysine, leucine, histidine, glutamine, arginine, isoleucine, methionine, valine, and phenylalanine, also showed significantly elevated levels. Citric acid administration significantly increased the levels of initial TCA cycle metabolites in the plasma. This increase after administration of citric acid was shown to be opposite to the metabolic changes observed in patients with CFS. These results contribute novel insight into the fatigue alleviation mechanism of citric acid.
最近的研究报道，慢性疲劳综合征（CFS）患者以及健康人运动后，血浆中三羧酸（TCA）循环代谢物和TCA循环相关代谢物的水平会发生变化。据报道，外源性膳食柠檬酸可缓解日常活动期间及运动后的疲劳。然而，膳食柠檬酸是否会影响这些代谢物的血浆水平尚不清楚。因此，本研究旨在探讨外源性给予柠檬酸对血浆中TCA循环代谢物和TCA循环相关代谢物的影响。将Sprague-Dawley大鼠分为对照组和柠檬酸组。我们使用液相色谱-串联质谱法（LC-MS/MS）通过代谢组学分析评估外源性膳食柠檬酸对血浆TCA循环及TCA循环相关代谢物的影响。外源性给予柠檬酸后，包括血浆柠檬酸、顺乌头酸和异柠檬酸在内的TCA循环代谢物显著升高。可转化为TCA循环代谢物的回补氨基酸，如丝氨酸、甘氨酸、色氨酸、赖氨酸、亮氨酸、组氨酸、谷氨酰胺、精氨酸、异亮氨酸, 蛋氨酸、缬氨酸和苯丙氨酸，其水平也显著升高。给予柠檬酸显著提高了血浆中初始TCA循环代谢物的水平。柠檬酸给药后的这种增加与CFS患者中观察到的代谢变化相反。这些结果为柠檬酸缓解疲劳的机制提供了新的见解。
