Endogenous conversion of n-6 to n-3 polyunsaturated fatty acids attenuates K/BxN serum-transfer arthritis in fat-1 mice

J Nutr Biochem. 2015 Jul;26(7):713-20. doi: 10.1016/j.jnutbio.2015.01.011. Epub 2015 Mar 20.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antirheumatic Agents / metabolism
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Experimental / diet therapy
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / prevention & control*
  • Arthritis, Rheumatoid / diet therapy
  • Arthritis, Rheumatoid / metabolism
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / prevention & control*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Cells, Cultured
  • Dietary Fats, Unsaturated / metabolism
  • Dietary Fats, Unsaturated / therapeutic use
  • Dietary Supplements
  • Fatty Acid Desaturases / genetics
  • Fatty Acid Desaturases / metabolism*
  • Fatty Acids, Omega-3 / metabolism*
  • Fatty Acids, Omega-3 / therapeutic use
  • Fatty Acids, Omega-6 / metabolism*
  • Humans
  • Interleukin-6 / metabolism
  • MAP Kinase Signaling System
  • Mice, Transgenic
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Recombinant Proteins / metabolism
  • STAT3 Transcription Factor / metabolism
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism*
  • Synovial Membrane / pathology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antirheumatic Agents
  • Caenorhabditis elegans Proteins
  • Dietary Fats, Unsaturated
  • Fatty Acids, Omega-3
  • Fatty Acids, Omega-6
  • Interleukin-6
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • fat-1 protein, C elegans
  • interleukin-6, mouse
  • Fatty Acid Desaturases