Metabolic profiling of synovial tissue shows altered glucose and choline metabolism in rheumatoid arthritis samples

Volchenkov, Roman; Cao, Maria Dung; Elgstøen, Katja Benedikte Prestø; Goll, G. L.; Eikvar, K; Bjørneboe, Olav; Bathen, T.F.; Holen, HL; Kvien, TK; Skålhegg, BS

doi:10.3109/03009742.2016.1164242

Cited by 24 publications

(22 citation statements)

References 5 publications

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“…Metabolomics profiling has shown alterations in the lipid metabolism in RA versus OA FLS. In line with this evidence, choline and choline like transporter (CTL)1 (high-affinity) and CTL2 (low affinity), were found to be highly expressed by synovial RA FLS (Ahn et al, 2016;Volchenkov et al, 2017) and their functional inhibition promoted FLS cell death (Seki et al, 2017). Supporting these findings, positron emission tomography (PET) scanning with 11 C-choline showed increased uptake in inflamed arthritic joints (Seki et al, 2017).…”

Section: Lipid Metabolismmentioning

confidence: 57%

Metabolic Checkpoints in Rheumatoid Arthritis

et al. 2020

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Several studies have highlighted the interplay between metabolism, immunity and inflammation. Both tissue resident and infiltrating immune cells play a major role in the inflammatory process of rheumatoid arthritis (RA) via the production of cytokines, adipocytokines and metabolic intermediates. These functions are metabolically demanding and require the most efficient use of bioenergetic pathways. The synovial membrane is the primary site of inflammation in RA and exhibits distinctive histological patterns characterized by different metabolism, prognosis and response to treatment. In the RA synovium, the high energy demand by stromal and infiltrating immune cells, causes the accumulation of metabolites, and adipo-cytokines, which carry out signaling functions, as well as activating transcription factors which act as metabolic sensors. These events drive immune and joint-resident cells to acquire pro-inflammatory effector functions which in turn perpetuate chronic inflammation. Whether metabolic changes are a consequence of the disease or one of the causes of RA pathogenesis is still under investigation. This review covers our current knowledge of cell metabolism in RA. Understanding the intricate interactions between metabolic pathways and the inflammatory and immune responses will provide more awareness of the mechanisms underlying RA pathogenesis and will identify novel therapeutic options to treat this disease.

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Section: Lipid Metabolismmentioning

confidence: 57%

Metabolic Checkpoints in Rheumatoid Arthritis

et al. 2020

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“…We hypothesized that perturbations caused by inflamed synovial tissue will lead to changes that correlate with the concentrations of certain metabolites in the synovium that will be then reflected in blood serum. A recent publication on a study of metabolic profiling in the synovial tissue reported altered glucose and choline metabolism [ 34 ]. Both pathways have recently been involved in RA pathogenesis [ 27 , 34 , 35 ].…”

Section: Discussionmentioning

confidence: 99%

“…A recent publication on a study of metabolic profiling in the synovial tissue reported altered glucose and choline metabolism [ 34 ]. Both pathways have recently been involved in RA pathogenesis [ 27 , 34 , 35 ]. Choline levels in patients from our cohorts are decreased in blood compared to the normal range; this, along with an increased uptake in the joints on choline C-11 PET scanning in inflammatory arthritis [ 36 ] and high expression in fibrocyte-like synoviocytes (FLS) of choline like transporter (CTL)1 (high-affinity) and CTL2 (low-affinity) [ 37 ], suggest increased circulating choline uptake and consumption by the inflamed synovium.…”

Section: Discussionmentioning

confidence: 99%

Serum metabolomic profiling predicts synovial gene expression in rheumatoid arthritis

et al. 2018

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BackgroundMetabolomics is an emerging field of biomedical research that may offer a better understanding of the mechanisms of underlying conditions including inflammatory arthritis. Perturbations caused by inflamed synovial tissue can lead to correlated changes in concentrations of certain metabolites in the synovium and thereby function as potential biomarkers in blood. Here, we explore the hypothesis of whether characterization of patients’ metabolomic profiles in blood, utilizing 1H-nuclear magnetic resonance (NMR), predicts synovial marker profiling in rheumatoid arthritis (RA).MethodsNineteen active, seropositive patients with RA, on concomitant methotrexate, were studied. One of the involved joints was a knee or a wrist appropriate for arthroscopy. A Bruker Avance 700 MHz spectrometer was used to acquire NMR spectra of serum samples. Gene expression in synovial tissue obtained by arthroscopy was analyzed by real-time PCR. Data processing and statistical analysis were performed in Python and SPSS.ResultsAnalysis of the relationships between each synovial marker-metabolite pair using linear regression and controlling for age and gender revealed significant clustering within the data. We observed an association of serine/glycine/phenylalanine metabolism and aminoacyl-tRNA biosynthesis with lymphoid cell gene signature. Alanine/aspartate/glutamate metabolism and choline-derived metabolites correlated with TNF-α synovial expression. Circulating ketone bodies were associated with gene expression of synovial metalloproteinases. Discriminant analysis identified serum metabolites that classified patients according to their synovial marker levels.ConclusionThe relationship between serum metabolite profiles and synovial biomarker profiling suggests that NMR may be a promising tool for predicting specific pathogenic pathways in the inflamed synovium of patients with RA.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1655-3) contains supplementary material, which is available to authorized users.

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“…Another potential factor that determines the concentrations of the circulating metabolites is represented by the release of metabolites from the inflamed joint or their uptake by the synovium. Little is known about metabolic or lipidomic profiling of synovial tissue [137,138]. In addition, no study has, to date, evaluated the relation between circulating metabolites in serum or plasma and synovial metabolites, although there might be a correlation.…”

Section: Metabolite Released From or Uptaken By Inflamed Tissuesmentioning

confidence: 99%

“…In addition, no study has, to date, evaluated the relation between circulating metabolites in serum or plasma and synovial metabolites, although there might be a correlation. For instance, the synovial tissue of RA patients presents an enhanced level of lactate compared to noninflamed synovial tissue [138], which suggests an increase in the anaerobic cellular metabolism of resident cells [139,140]. Lactate has also been one of the metabolites described to be upregulated in patients with RA [5].…”

Section: Metabolite Released From or Uptaken By Inflamed Tissuesmentioning

confidence: 99%

Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

Coras

Murillo-Saich

Gumá

2020

Cells

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Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects synovial joints, leading to inflammation, joint destruction, loss of function, and disability. Although recent pharmaceutical advances have improved the treatment of RA, patients often inquire about dietary interventions to improve RA symptoms, as they perceive pain and/or swelling after the consumption or avoidance of certain foods. There is evidence that some foods have pro- or anti-inflammatory effects mediated by diet-related metabolites. In addition, recent literature has shown a link between diet-related metabolites and microbiome changes, since the gut microbiome is involved in the metabolism of some dietary ingredients. But diet and the gut microbiome are not the only factors linked to circulating pro- and anti-inflammatory metabolites. Other factors including smoking, associated comorbidities, and therapeutic drugs might also modify the circulating metabolomic profile and play a role in RA pathogenesis. This article summarizes what is known about circulating pro- and anti-inflammatory metabolites in RA. It also emphasizes factors that might be involved in their circulating concentrations and diet-related metabolites with a beneficial effect in RA.

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Metabolic profiling of synovial tissue shows altered glucose and choline metabolism in rheumatoid arthritis samples

Cited by 24 publications

References 5 publications

Metabolic Checkpoints in Rheumatoid Arthritis

Metabolic Checkpoints in Rheumatoid Arthritis

Serum metabolomic profiling predicts synovial gene expression in rheumatoid arthritis

Circulating Pro- and Anti-Inflammatory Metabolites and Its Potential Role in Rheumatoid Arthritis Pathogenesis

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