Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats

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 dail...

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Main Authors: Yurie Hara, Satoshi Kume, Yosky Kataoka, Nakamichi Watanabe
Format: Article
Language:English
Published: Elsevier 2021-12-01
Series:Heliyon
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844021026049
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author Yurie Hara
Satoshi Kume
Yosky Kataoka
Nakamichi Watanabe
author_facet Yurie Hara
Satoshi Kume
Yosky Kataoka
Nakamichi Watanabe
author_sort Yurie Hara
collection DOAJ
description 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.
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spelling doaj.art-ec372cba89a346c79c484cf67a7594242022-12-21T23:27:27ZengElsevierHeliyon2405-84402021-12-01712e08501Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in ratsYurie Hara0Satoshi Kume1Yosky Kataoka2Nakamichi Watanabe3Department of Advanced Food Sciences, College of Agriculture, Tamagawa University, Tokyo, JapanLaboratory for Pathophysiological and Health Science, RIKEN Center for Biosystems Dynamics Research, Kobe, Japan; Center for Health Science Innovation, Osaka City University, Osaka, Japan; Laboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Hyogo, JapanLaboratory for Cellular Function Imaging, RIKEN Center for Biosystems Dynamics Research, Hyogo, Japan; Multi-modal Microstructure Analysis Unit, RIKEN-JEOL Collaboration Center, RIKEN Baton Zone Program, Hyogo, JapanDepartment of Health Science, Faculty of Food and Health Sciences, Showa Women's University, Tokyo, Japan; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2405844021026049Citric acidFatigueTricarboxylic acid cycleAmino acidAnaplerotic substratesMetabolome analysis
spellingShingle Yurie Hara
Satoshi Kume
Yosky Kataoka
Nakamichi Watanabe
Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats
Heliyon
Citric acid
Fatigue
Tricarboxylic acid cycle
Amino acid
Anaplerotic substrates
Metabolome analysis
title Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats
title_full Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats
title_fullStr Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats
title_full_unstemmed Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats
title_short Changes in TCA cycle and TCA cycle-related metabolites in plasma upon citric acid administration in rats
title_sort changes in tca cycle and tca cycle related metabolites in plasma upon citric acid administration in rats
topic Citric acid
Fatigue
Tricarboxylic acid cycle
Amino acid
Anaplerotic substrates
Metabolome analysis
url http://www.sciencedirect.com/science/article/pii/S2405844021026049
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AT yoskykataoka changesintcacycleandtcacyclerelatedmetabolitesinplasmauponcitricacidadministrationinrats
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