4.8 Review

Lipid metabolism and rheumatoid arthritis

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Review Cell Biology

Role of T Cells in the Pathogenesis of Rheumatoid Arthritis: Focus on Immunometabolism Dysfunctions

Maryam Masoumi et al.

Summary: Evidence has shown that metabolic-associated T cell abnormalities can be detected in the early stages of rheumatoid arthritis (RA) development. Molecular evaluations have revealed changes in metabolic pathways in RA T cells, leading to an aggressive phenotype. Many genes involved in metabolic pathways exhibit abnormal expression in RA T cells. Additionally, metabolic alterations affect DNA repair and fatty acid oxidation pathways, which impact the functionality and invasive phenotype of RA T cells. Understanding the role of metabolic pathways in RA pathogenesis can provide insights into the interactions between the environment, genes, and host/microbiota, and aid in the development of potential therapeutic approaches.

INFLAMMATION (2023)

Review Biochemistry & Molecular Biology

Lipid metabolism within the bone micro-environment is closely associated with bone metabolism in physiological and pathophysiological stages

Bo Wang et al.

Summary: Recent advances in society have led to the emergence of hyperlipidemia and obesity as life-threatening conditions. Aging population, especially menopausal women, often suffer from overweight and bone loss simultaneously. Clinical observations suggest a link between osteoarthritis and higher BMI. Bone serves as a mechanical organ and plays critical roles in metabolism and endocrine functions.

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Review Rheumatology

Janus kinase-targeting therapies in rheumatology: a mechanisms-based approach

Yoshiya Tanaka et al.

Summary: This Review discusses the therapeutic use of Janus kinase inhibitors in autoimmune rheumatic diseases, highlighting their disease-specific mechanisms of action. JAK inhibitors suppress intracellular signaling mediated by multiple cytokines, offering potential treatment options for a range of immune and inflammatory disorders.

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Review Cardiac & Cardiovascular Systems

Triggers of Cardiovascular Diseases in Rheumatoid Arthritis

Mei Zhang et al.

Summary: The risk of cardiovascular disease is higher in patients with rheumatoid arthritis compared to those without RA, even higher than patients with diabetes. The mechanism of early cardiac dysfunction in RA may occur prior to atherosclerosis. Clear biomarkers and treatment goals for cardiovascular risk factors in RA are currently lacking.

CURRENT PROBLEMS IN CARDIOLOGY (2022)

Article Immunology

CPT1A-Mediated Fatty Acid Oxidation Promotes Precursor Osteoclast Fusion in Rheumatoid Arthritis

Zhaoyang Huang et al.

Summary: This study reveals a new mechanism through which fatty acid oxidation metabolism contributes to joint destruction in rheumatoid arthritis (RA). Increasing fatty acid oxidation leads to fusion of osteoclast precursors and enhances clathrin-dependent endocytosis pathway, resulting in bone destruction. This study provides a novel therapeutic direction for the development of drugs against bone destruction in patients with RA.

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Article Pharmacology & Pharmacy

Short-chain fatty acids regulate B cells differentiation via the FFA2 receptor to alleviate rheumatoid arthritis

Yao Yao et al.

Summary: Short-chain fatty acids regulate B cell differentiation via FFA2 receptors to alleviate rheumatoid arthritis, providing new insights into the treatment of RA from an immunological and microbiological perspective.

BRITISH JOURNAL OF PHARMACOLOGY (2022)

Article Rheumatology

Imbalance of Th17, Treg, and helper innate lymphoid cell in the peripheral blood of patients with rheumatoid arthritis

Ting Wang et al.

Summary: The study found that RA patients had higher proportions of immune cells CD4(+) T, CD19(+) B, Th17, ILC2, and ILC3 compared to healthy controls, while lower proportions of Treg and ILC1. RA patients also had higher levels of IFN-gamma, IL-4, IL-17A, and IL-22 and lower levels of IL-10. Patients with high disease activity showed even higher proportions of Th17, ILC2, and ILC3, and lower proportions of ILC1 and Treg.

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Article Nutrition & Dietetics

Serum Fatty Acid Profiles Are Associated with Disease Activity in Early Rheumatoid Arthritis: Results from the ESPOIR Cohort

Johanna Sigaux et al.

Summary: This study aimed to investigate the relationship between serum lipid profiles and disease activity in patients with early rheumatoid arthritis (RA). The study found that a serum lipid profile rich in n-3 fatty acids was independently associated with persistently reduced disease activity, while a profile rich in n-6 fatty acids was associated with lower disease activity.

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Article Immunology

Advance in bone destruction participated by JAK/STAT in rheumatoid arthritis and therapeutic effect of JAK/STAT inhibitors

Ling Hu et al.

Summary: This article reviews the research progress of bone destruction mediated by JAK/STAT in rheumatoid arthritis and the therapeutic effects of JAK/STAT inhibitors.

INTERNATIONAL IMMUNOPHARMACOLOGY (2022)

Article Biochemistry & Molecular Biology

Lipoxin A4-Mediated p38 MAPK Signaling Pathway Protects Mice Against Collagen-Induced Arthritis

Jinyu Li et al.

Summary: This study found that LXA4 could protect CIA mice by inhibiting p38 MAPK pathway, reducing synoviocyte proliferation, decreasing inflammatory cytokine levels, alleviating oxidative stress, and easing arthritis severity.

BIOCHEMICAL GENETICS (2021)

Review Biochemistry & Molecular Biology

Shaping of Monocyte-Derived Dendritic Cell Development and Function by Environmental Factors in Rheumatoid Arthritis

Frederic Coutant

Summary: Dendritic cells play a crucial role in both immunity and immune tolerance, with their function and distribution being severely affected in chronic inflammatory diseases like rheumatoid arthritis (RA). In RA, environmental factors in the joint impact the development of Mo-DC, contributing to defective tolerance and inflammation. Understanding the molecular signaling pathways controlling Mo-DC differentiation could lead to breakthroughs in new therapies for RA.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Rheumatology

Divergence of Cardiovascular Biomarkers of Lipids and Subclinical Myocardial Injury Among Rheumatoid Arthritis Patients With Increased Inflammation

Brittany Weber et al.

Summary: RA patients with increased inflammation showed significant decreases in lipid levels, including LDL cholesterol, and increases in markers of subclinical myocardial injury. This suggests a divergence in CVD risk biomarkers and potential utility of hs-cTnT in future studies for CVD risk stratification in RA patients.

ARTHRITIS & RHEUMATOLOGY (2021)

Article Physiology

Treatment With Coenzyme Q10, ω-3-Polyunsaturated Fatty Acids and Their Combination Improved Bioenergetics and Levels of Coenzyme Q9 and Q10 in Skeletal Muscle Mitochondria in Experimental Model of Arthritis

Jarmila Kucharska et al.

Summary: The study evaluated the effects of CoQ(10) and omega-3-PUFA monotherapy and combination therapy in adjuvant arthritis, showing that the combined treatment is more effective in improving mitochondrial function, inflammation, and antioxidant status compared to monotherapy.

PHYSIOLOGICAL RESEARCH (2021)

Article Multidisciplinary Sciences

Arachidonic acid-regulated calcium signaling in T cells from patients with rheumatoid arthritis promotes synovial inflammation

Zhongde Ye et al.

Summary: In this study, it was shown that CD4(+) T cells from patients with RA and PsA have increased expression of the pore-forming calcium channel component ORAI3 due to reduced IKAROS expression, leading to increased ARC channel activity and sensitivity to arachidonic acid. This heightened activity may contribute to chronic inflammation in these conditions, indicating a potential mechanism for the pathogenesis of RA and PsA.

NATURE COMMUNICATIONS (2021)

Review Immunology

RORγt protein modifications and IL-17-mediated inflammation

Ritesh Kumar et al.

Summary: ROR gamma t plays a crucial role in regulating IL-17-driven inflammation through multiple post-translational modifications. Understanding these pathways is essential for studying the pathogenic role of ROR gamma t+IL-17+ cells and developing potential therapeutic strategies.

TRENDS IN IMMUNOLOGY (2021)

Review Immunology

B Cells in Rheumatoid Arthritis:Pathogenic Mechanisms and Treatment Prospects

Fengping Wu et al.

Summary: Rheumatoid arthritis is a common, chronic, systemic autoimmune disease characterized by immune system disorders, with autoreactive CD4(+)T cells, pathogenic B cells, and inflammatory cytokines being key players. Further research is needed to distinguish between pathogenic B cells and protective B cells in patients with RA to develop more targeted treatments.

FRONTIERS IN IMMUNOLOGY (2021)

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Evaluation of dysfunctional high-density lipoprotein levels with myeloperoxidase/paraoxonase-1 ratio in rheumatoid arthritis

Tugba Alisik et al.

Summary: Higher MPO/PON1 ratio in rheumatoid arthritis (RA) patients may be associated with increased cardiovascular disease (CVD) risk. The dysfunction of HDL in RA patients, as indicated by the MPO/PON1 ratio, suggests potential implications for assessing cardiovascular risk and monitoring treatment effectiveness in this population.

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE (2021)

Review Biochemistry & Molecular Biology

Biomarkers in Prostate Cancer Diagnosis: From Current Knowledge to the Role of Metabolomics and Exosomes

Stefano Salciccia et al.

Summary: Early detection of prostate cancer relies on PSA levels, but it lacks the ability to distinguish between benign and clinically significant forms of the disease. New urinary and serum biomarkers have been developed, but specific guidelines on their use are currently lacking.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

Article Biochemistry & Molecular Biology

Plasma Metabolome Normalization in Rheumatoid Arthritis Following Initiation of Methotrexate and the Identification of Metabolic Biomarkers of Efficacy

Matthew R. Medcalf et al.

Summary: The study found that RA patients have altered plasma metabolome which is partially normalized following initiation of MTX therapy. Different metabolites were found to be impacted in responders and non-responders to MTX therapy.

METABOLITES (2021)

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Prediction of response of methotrexate in patients with rheumatoid arthritis using serum lipidomics

Mateusz Maciejewski et al.

Summary: Methotrexate is a common first-line treatment for rheumatoid arthritis, but it is ineffective for a significant portion of patients, with no reliable way to predict individual responses. Statistical models based on serum lipid levels were explored for predicting methotrexate response in patients, but clinical covariates alone outperformed lipid-based models in predicting response. Serum lipid profiles at pre-treatment or early-treatment time points are unlikely to be predictive of methotrexate response by 6 months in a way that would be useful for clinical management of rheumatoid arthritis.

SCIENTIFIC REPORTS (2021)

Article Rheumatology

Fatty Acids and Oxylipins in Osteoarthritis and Rheumatoid Arthritis-a Complex Field with Significant Potential for Future Treatments

Anne-Mari Mustonen et al.

Summary: OA and RA are characterized by abnormal lipid metabolism with altered FA profiles in synovial fluid and tissues. Dietary FA supplements, especially long-chain n-3 PUFA, have positive effects on joint health, while n-6 PUFA may have mixed effects. SPM analogs have potential as analgesics for arthritic pain.

CURRENT RHEUMATOLOGY REPORTS (2021)

Review Immunology

Metabolic Control of Autoimmunity and Tissue Inflammation in Rheumatoid Arthritis

Jingtao Qiu et al.

Summary: Rheumatoid arthritis (RA) develops in three distinct stages, involving dysfunction of T cells and B cells, tissue invasion, and tissue destruction. Metabolic mis-regulation is a key pathogenic pathway in all phases of RA, with defective DNA repair and misbalanced metabolic pathways contributing to autoimmunity and tissue inflammation. Targeting metabolic abnormalities may offer a novel treatment strategy for autoimmune diseases like RA.

FRONTIERS IN IMMUNOLOGY (2021)

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Synovial Fluid Fatty Acid Profiles Are Differently Altered by Inflammatory Joint Pathologies in the Shoulder and Knee Joints

Anne-Mari Mustonen et al.

Summary: Anomalies in fatty acid metabolism are characteristic of osteoarthritis and rheumatoid arthritis in the knee joint. A study compared fatty acid alterations in the synovial fluid of shoulder and knee joints in trauma controls and patients with end-stage arthritis. The results showed location- and disease-dependent differences in fatty acid composition.

BIOLOGY-BASEL (2021)

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Vascular cell adhesion molecule-1 in rheumatoid arthritis patients Relation to disease activity, oxidative stress, and systemic inflammation

Heba R. Salem et al.

Summary: The study revealed that RA patients had higher levels of serum VCAM-1, malondialdehyde, ESR, and C-reactive protein, while showing lower total antioxidant capacity and high-density lipoprotein levels. Serum VCAM-1 was positively correlated with disease activity, oxidative stress, and inflammatory markers, and negatively correlated with total antioxidant capacity.

SAUDI MEDICAL JOURNAL (2021)

Article Nutrition & Dietetics

Increased Levels of Omega-3 Fatty Acids and DHA Are Linked to Pain Reduction in Rheumatoid Arthritis Patients Treated with Janus Kinase Inhibitors

Ching-Kun Chang et al.

Summary: The study found that treatment with Janus kinase inhibitors may reduce pain in rheumatoid arthritis patients by increasing levels of omega-3 fatty acids and DHA.

NUTRIENTS (2021)

Article Rheumatology

A bioavailable form of curcumin, in combination with vitamin-D- and omega-3-enriched diet, modifies disease onset and outcomes in a murine model of collagen-induced arthritis

Mahadevappa Hemshekhar et al.

Summary: The combination of highly bioavailable curcumin, vitamin D-3, and omega-3 fatty acids significantly delays and reduces the development of collagen-induced arthritis (CIA). This study suggests a rationale for systematically evaluating these widely available supplements in individuals at risk for developing rheumatoid arthritis.

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The metabolic signature of T cells in rheumatoid arthritis

Cornelia M. Weyand et al.

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Dual Role of Chondrocytes in Rheumatoid Arthritis: The Chicken and the Egg

Chia-Chun Tseng et al.

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Could Omega 3 Fatty Acids Preserve Muscle Health in Rheumatoid Arthritis?

Kassandra Lanchais et al.

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High density lipoprotein in rheumatoid arthritis: emerging role in predicting inflammation level and osteoporosis occurrence

Tingting Zeng et al.

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Klaus W. Frommer et al.

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Abnormal lipid metabolism in a rat model of arthritis: one possible pathway

Niraj Kumar Srivastava et al.

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Russell A. DeBose-Boyd

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Maresin 1 improves the Treg/Th17 imbalance in rheumatoid arthritis through miR-21

Shengwei Jin et al.

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Association of serum lipids with autoantibodies and inflammatory markers in rheumatoid arthritis patients

Longjie Gan et al.

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Jillian P. Rhoads et al.

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Jae-hyuck Shim et al.

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Qiang Guo et al.

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Cynthia S. Crowson et al.

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Altered gut microbiota in RA: implications for treatment

Y. Kang et al.

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Use of Hydroxychloroquine Is Associated With Improved Lipid Profile in Rheumatoid Arthritis Patients

Jose Felix Restrepo et al.

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Luca Navarini et al.

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Mozghan Abdulrazaq et al.

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Yoshishige Miyabe et al.

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Marta F. Bustamante et al.

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Kevin D. Deane et al.

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Julia Schumann

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Resolvin D3 Is Dysregulated in Arthritis and Reduces Arthritic Inflammation

Hildur H. Arnardottir et al.

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Maria C. Basil et al.

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Hilde Brouwers et al.

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Catherine M. McGrath et al.

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Klaus W. Frommer et al.

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A comparative study on serum lipoprotein (a) and lipid profile between rheumatoid arthritis patients and normal subjects

K. P. Shiva Govindan et al.

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Lipid and lipid mediator profiling of human synovial fluid in rheumatoid arthritis patients by means of LC-MS/MS

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