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2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver

Rheumatoid arthritis (RA) is significantly associated with glycolysis. This study used 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, to treat rats with collagen-induced arthritis (CIA) and investigate the metabolic regulatory mechanism of glycolysis in the disease. 2-DG significantly allevia...

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Autores principales: Wang, Hongxing, Zhang, Nanyang, Fang, Kehua, Chang, Xiaotian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440946/
https://www.ncbi.nlm.nih.gov/pubmed/34539643
http://dx.doi.org/10.3389/fimmu.2021.713799
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author Wang, Hongxing
Zhang, Nanyang
Fang, Kehua
Chang, Xiaotian
author_facet Wang, Hongxing
Zhang, Nanyang
Fang, Kehua
Chang, Xiaotian
author_sort Wang, Hongxing
collection PubMed
description Rheumatoid arthritis (RA) is significantly associated with glycolysis. This study used 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, to treat rats with collagen-induced arthritis (CIA) and investigate the metabolic regulatory mechanism of glycolysis in the disease. 2-DG significantly alleviated CIA. Metabolomics and transcriptomics, as well as their integrative analysis, detected significant changes in the pathways of bile secretion, cholesterol and linoleic acid metabolism in the plasma, liver and spleen during the CIA process and the opposite changes following 2-DG treatment, whereas the expression of the genes regulating these metabolic pathways were changed only in the spleen. In the rat liver, levels of (S)-5-diphosphomevalonic acid in the terpenoid backbone biosynthesis pathway were significantly decreased during CIA progression and increased following 2-DG treatment, and levels of taurochenodeoxycholic acid in the pentose and glucuronate interconversions pathway showed the opposite results. In the spleen, levels of 3-methoxy-4-hydroxyphenylglycol glucuronide in bile secretion and 12(S)-leukotriene B4 in arachidonic acid metabolism were significantly decreased during CIA progression and increased following 2-DG treatment. The changes in the gene-metabolite network of bile secretion in the spleen correlated with a decreased plasma L-acetylcarnitine level in CIA rats and an increase following 2-DG treatment. Our analysis suggests the involvement of spleen and liver metabolism in CIA under the control of glycolysis.
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spelling pubmed-84409462021-09-16 2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver Wang, Hongxing Zhang, Nanyang Fang, Kehua Chang, Xiaotian Front Immunol Immunology Rheumatoid arthritis (RA) is significantly associated with glycolysis. This study used 2-deoxy-D-glucose (2-DG), an inhibitor of glycolysis, to treat rats with collagen-induced arthritis (CIA) and investigate the metabolic regulatory mechanism of glycolysis in the disease. 2-DG significantly alleviated CIA. Metabolomics and transcriptomics, as well as their integrative analysis, detected significant changes in the pathways of bile secretion, cholesterol and linoleic acid metabolism in the plasma, liver and spleen during the CIA process and the opposite changes following 2-DG treatment, whereas the expression of the genes regulating these metabolic pathways were changed only in the spleen. In the rat liver, levels of (S)-5-diphosphomevalonic acid in the terpenoid backbone biosynthesis pathway were significantly decreased during CIA progression and increased following 2-DG treatment, and levels of taurochenodeoxycholic acid in the pentose and glucuronate interconversions pathway showed the opposite results. In the spleen, levels of 3-methoxy-4-hydroxyphenylglycol glucuronide in bile secretion and 12(S)-leukotriene B4 in arachidonic acid metabolism were significantly decreased during CIA progression and increased following 2-DG treatment. The changes in the gene-metabolite network of bile secretion in the spleen correlated with a decreased plasma L-acetylcarnitine level in CIA rats and an increase following 2-DG treatment. Our analysis suggests the involvement of spleen and liver metabolism in CIA under the control of glycolysis. Frontiers Media S.A. 2021-09-01 /pmc/articles/PMC8440946/ /pubmed/34539643 http://dx.doi.org/10.3389/fimmu.2021.713799 Text en Copyright © 2021 Wang, Zhang, Fang and Chang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wang, Hongxing
Zhang, Nanyang
Fang, Kehua
Chang, Xiaotian
2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver
title 2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver
title_full 2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver
title_fullStr 2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver
title_full_unstemmed 2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver
title_short 2-Deoxy-D-glucose Alleviates Collagen-Induced Arthritis of Rats and Is Accompanied by Metabolic Regulation of the Spleen and Liver
title_sort 2-deoxy-d-glucose alleviates collagen-induced arthritis of rats and is accompanied by metabolic regulation of the spleen and liver
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440946/
https://www.ncbi.nlm.nih.gov/pubmed/34539643
http://dx.doi.org/10.3389/fimmu.2021.713799
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