Abstract
It is suggested that n-3 polyunsaturated fatty acids (PUFAs) can be used in the preventive or therapeutic management of rheumatoid arthritis (RA); however, controversial results have been reported. Here, we examined the effects of a decrease in the n-6/n-3 PUFA ratio on RA using fat-1 transgenic mice. First, we tested whether fat-1 expression modulated signaling pathways in fibroblast-like synoviocytes (FLSs) stimulated with tumor necrosis factor α (TNF-α). TNF-α activated p38 mitogen-activated protein kinase and increased phosphorylation of the signal transducer and activator of transcription 3 in wild type (WT) FLSs but not in fat-1 FLSs. Arthritis was induced by injection of K/BxN serum. Based on clinical scores, ankle thickness and pathological severity, we showed that WT mice developed clinically overt arthritis, whereas fat-1 mice showed attenuated arthritis. Moreover, fat-1 mice exhibited down-regulated local and systemic levels of inflammatory cytokines. Lastly, bone marrow-derived macrophages (BMMs) of WT mice differentiated into tartrate-resistant acid phosphatase-positive multinucleated osteoclasts, whereas the osteoclastogenenic process was suppressed in BMMs of fat-1 mice. The endogenous conversion of n-6 to n-3 PUFAs via fat-1 plays a key role in attenuation of RA; therefore, dietary supplementation of n-3 PUFAs may have therapeutic potential for the management of RA.
Keywords:
IL-6; K/BxN; RA; fat-1; n-3 PUFA.
Copyright © 2015 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antirheumatic Agents / metabolism
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Antirheumatic Agents / therapeutic use
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Arthritis, Experimental / diet therapy
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Arthritis, Experimental / metabolism
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Arthritis, Experimental / pathology
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Arthritis, Experimental / prevention & control*
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Arthritis, Rheumatoid / diet therapy
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Arthritis, Rheumatoid / metabolism
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Arthritis, Rheumatoid / pathology
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Arthritis, Rheumatoid / prevention & control*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Cells, Cultured
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Dietary Fats, Unsaturated / metabolism
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Dietary Fats, Unsaturated / therapeutic use
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Dietary Supplements
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Fatty Acid Desaturases / genetics
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Fatty Acid Desaturases / metabolism*
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Fatty Acids, Omega-3 / metabolism*
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Fatty Acids, Omega-3 / therapeutic use
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Fatty Acids, Omega-6 / metabolism*
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Humans
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Interleukin-6 / metabolism
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MAP Kinase Signaling System
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Mice, Transgenic
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Phosphorylation
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Protein Processing, Post-Translational
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Recombinant Proteins / metabolism
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STAT3 Transcription Factor / metabolism
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Synovial Membrane / cytology
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Synovial Membrane / immunology
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Synovial Membrane / metabolism*
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Synovial Membrane / pathology
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antirheumatic Agents
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Caenorhabditis elegans Proteins
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Dietary Fats, Unsaturated
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Fatty Acids, Omega-3
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Fatty Acids, Omega-6
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Interleukin-6
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Recombinant Proteins
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STAT3 Transcription Factor
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Stat3 protein, mouse
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TNF protein, human
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Tumor Necrosis Factor-alpha
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fat-1 protein, C elegans
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interleukin-6, mouse
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Fatty Acid Desaturases