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

Abstract

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.

Raman spectroscopy as a promising diagnostic method for rheumatoid arthritis

“…31 Further evidence that an inhibitor of glycolysis significantly ameliorated collagen-induced arthritis confirmed this. 32 As for glycogen, one explanation for this change observed in the Raman spectra could be that glycogen accumulation in the synovial tissue of RA was due to synovial inflammation. 33…”

“…31 Further evidence that an inhibitor of glycolysis signicantly ameliorated collageninduced arthritis conrmed this. 32 As for glycogen, one explanation for this change observed in the Raman spectra could be that glycogen accumulation in the synovial tissue of RA was due to synovial inammation. 33 The clinical manifestations, etiology, and pathogenesis of ACPA-positive RA and ACPA-negative RA, especially how they differ and what they have in common, still need to be further explored.…”

Metabolomics in rheumatoid arthritis: Advances and review

“…Additionally, further studies of other rheumatoid immune diseases are needed to demonstrate the effectiveness of the diagnosis biomarkers. Metabolic changes that participate in the pathogenesis of RA can provide a mechanism and rationale for treatment administration, such as glucose deprivation or glycolytic inhibitors ( 126 , 127 ). Novel sensitive therapeutics can be developed to target key enzymes in metabolic pathways.…”

Glycolysis in Innate Immune Cells Contributes to Autoimmunity

“…Hallmark lesion sites represent not only differences in clinical symptoms but also differences in metabolic abnormalities. For example, expression signatures in III/IV lupus nephritis tubulointerstitium exhibit down-regulated glycolytic activity (79) while increased glucose uptake and glycolysis are observed in RA-lesioned joints (80). Additionally, glycolysis in diverse stages contributes to the development of AIDs.…”