Adipokines in rheumatoid arthritis

Fatel, Elis Carolina de Souza; Rosa, Francisco Dalla; Simão, Andréa Name Colado; Dichi, Isaías

doi:10.1186/s42358-018-0026-8

Cited by 54 publications

(90 citation statements)

References 67 publications

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“…Other receptors such as T cadherin [57,58,59,60] and PAQR3 [61] have also been discussed. Mainly anti-inflammatory effects at the systemic level have been described for adiponectin in atherosclerosis but also for example in metabolic syndrome, type 2 diabetes mellitus [56,62]. In contrast, adiponectin seems to have opposing effects on effector cells of arthritis.…”

Section: Adiponectinmentioning

confidence: 99%

“…Numerous studies found that cultured RASF respond to adiponectin by an increase of pro-inflammatory factors including prostaglandin E2, IL-6, IL-8, MMPs-1, -13 [56,62]. However, a stronger pro-inflammatory effect of the HMW isoforms has been described in contrast to LMW adiponectin in these cells [56,62]. For some cell types, even opposing effects have been described for specific adiponectin isoforms.…”

Section: Adiponectinmentioning

confidence: 99%

“…For example, IL-6 secretion was induced by HMW adiponectin in human monocytes (but had no such effect on lipopolysaccharide (LPS)-activated monocytes), while LMW adiponectin reduced IL-6 and increased IL-10 secretion in LPS-activated monocytes [63]. Other cell types including chondrocytes, endothelial cells and lymphocytes showed a mainly pro-inflammatory response to adiponectin [56,62]. Bone cells are affected as well by adiponectin in both OA and RA [15].…”

Section: Adiponectinmentioning

confidence: 99%

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The Adipokine Network in Rheumatic Joint Diseases

Carrión

Frommer

Pérez‐García

et al. 2019

IJMS

134

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Rheumatic diseases encompass a diverse group of chronic disorders that commonly affect musculoskeletal structures. Osteoarthritis (OA) and rheumatoid arthritis (RA) are the two most common, leading to considerable functional limitations and irreversible disability when patients are unsuccessfully treated. Although the specific causes of many rheumatic conditions remain unknown, it is generally accepted that immune mechanisms and/or uncontrolled inflammatory responses are involved in their etiology and symptomatology. In this regard, the bidirectional communication between neuroendocrine and immune system has been demonstrated to provide a homeostatic network that is involved in several pathological conditions. Adipokines represent a wide variety of bioactive, immune and inflammatory mediators mainly released by adipocytes that act as signal molecules in the neuroendocrine-immune interactions. Adipokines can also be synthesized by synoviocytes, osteoclasts, osteoblasts, chondrocytes and inflammatory cells in the joint microenvironment, showing potent modulatory properties on different effector cells in OA and RA pathogenesis. Effects of adiponectin, leptin, resistin and visfatin on local and systemic inflammation are broadly described. However, more recently, other adipokines, such as progranulin, chemerin, lipocalin-2, vaspin, omentin-1 and nesfatin, have been recognized to display immunomodulatory actions in rheumatic diseases. This review highlights the latest relevant findings on the role of the adipokine network in the pathophysiology of OA and RA.

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Section: Adiponectinmentioning

confidence: 99%

Section: Adiponectinmentioning

confidence: 99%

Section: Adiponectinmentioning

confidence: 99%

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The Adipokine Network in Rheumatic Joint Diseases

Carrión

Frommer

Pérez‐García

et al. 2019

IJMS

134

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“…Besides, plasma adiponectin levels have been associated with circulating inflammatory cytokines in a cohort of subjects at high risk to develop RA (20). Taken all together, those results suggest that adiponectin might be a factor implicated in the initiation and progression of RA (21).…”

Section: Introductionmentioning

confidence: 70%

Total and high-molecular weight plasma adiponectin associates with markers of inflammation and circulating chemokines in subjects with untreated newly diagnosed rheumatoid arthritis.

Vasileiadis

Lundell

Zhang

et al. 2020

Preprint

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Background Adiponectin is an adipokine circulating in blood in three forms, whereof the high molecular weight (HMW) is supposed to mediate the metabolic effects of adiponectin. Subjects with rheumatoid arthritis (RA) have elevated levels of adiponectin in serum and synovial fluid but it is unclear if circulating adiponectin associates with disease activity markers in subjects with RA. Here we aimed to determine whether total and/or HMW adiponectin levels associate with markers of disease activity and plasma chemokines in a cohort of subjects with untreated newly diagnosed RA.Methods Inflammation and disease activity were assessed in a cohort of 70 subjects with untreated newly diagnosed RA using erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), number of tender or swollen joints, as well as disease activity scores (DAS28 and CDAI) Plasma levels of 15 chemokines were measured using flow cytometry bead-based immunoassay or ELISA. Total and HMW adiponectin plasma levels were determined with ELISA.Results Both total and HMW adiponectin were positively associated with CRP (both P = 0.001) and ESR (P = 0.001 and P < 0.001 respectively). Furthermore, a positive association was found between total adiponectin and CXCL10 (P = 0.021), CCL2 (P = 0.012) and CXCL9 (P = 0.044), whereas HMW adiponectin associated with CXCL9 only (P = 0.033).Conclusion Total and HMW adiponectin are associated with markers of inflammation as well as pro-inflammatory chemokines in a cohort of 70 subjects with untreated newly diagnosed RA. Our results support the hypothesis that adiponectin might be a pro-inflammatory factor involved in the pathogenesis of RA.

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“…Several biological mechanisms have been proposed to interpret the potential effect of resistin on the pathogenesis of RA. It is widely recognized that RA is a persistent in ammatory diease, which is related to several in ammatory cytokines [39]. Šenolt et al reported that resistin was expressed in different in ammatory cells of RA synovial tissue, including macrophages (CD68), B lymphocytes (CD20) and plasma cells (CD138) [40].…”

Section: Discussionmentioning

confidence: 99%

Adipokines and risk of rheumatoid arthritis: a Mendelian randomization study

Zhu

Zheng

et al. 2020

Preprint

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Background: Circulating adipokines levels have been reported to be associated with the risk of rheumatoid arthritis (RA). However, it is still unclear whether these associations are causal or biased by reverse causation or residual confounding. This study aimed to assess potential causal roles of five adipokines (namely, adiponectin, leptin, resistin, chemerin, and retinol-blinding protein 4 [RBP4]) in the occurrence of RA.Methods: We conducted a two-sample Mendelian randomization analysis to investigate these associations. We used summary-level data from genome-wide association studies (GWASs) for adipokines in individuals of European ancestry as the exposure, and a separate large-scale meta-analysis of a GWAS which included 14,361 RA cases and 43,923 controls of European ancestry as the outcome. Genetic variants were selected as instrumental variables if robustly genome-wide significant in their associations with adipokines. The causal effects were estimated using the inverse-variance weighted method in the primary analysis. Sensitivity analyses were performed to warrant that bias due to genetic pleiotropy was unlikely.Results: The circulating resistin was found to be the only adipokinetic factor having statistical significance, with higher levels causally associated with the risk of RA (odds ratio: 1.28; 95% confidence interval: [1.07, 1.53] per unit increase in the natural log-transformed resistin). In contrast, associations of adiponectin, leptin, chemerin, and RBP4 with risk of RA were not statistically significant. The MR assumptions did not seem to be violated. Sensitivity analyses yielded consistent findings.Conclusions: Genetically predicted circulating resistin levels were positively associated with RA risk. Our analysis suggested that resistin may play a notable causal role in RA pathogenesis. It would be beneficial for the development of clinical as well as public health strategies that target appropriate levels of resistin for future RA intervention.

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Adipokines in rheumatoid arthritis

Cited by 54 publications

References 67 publications

The Adipokine Network in Rheumatic Joint Diseases

The Adipokine Network in Rheumatic Joint Diseases

Total and high-molecular weight plasma adiponectin associates with markers of inflammation and circulating chemokines in subjects with untreated newly diagnosed rheumatoid arthritis.

Adipokines and risk of rheumatoid arthritis: a Mendelian randomization study

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