title: Endogenous conversion of n-6 to n-3 polyunsaturated fatty acids attenuates K/BxN serum-transfer arthritis in fat-1 mice.
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.
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Seong Ji
authors.initials: SJ
authors.lastname: Woo
authors.affiliation: Department of Biochemistry and Cancer Research Institute, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea.
authors.forename: Kyu
authors.initials: K
authors.lastname: Lim
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Woosuk University, Wanju, Jeonbuk 565-701, Republic of Korea.
authors.forename: Su Yeon
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Food Science and Biotechnology, Graduate School, Woosuk University, Wanju, Jeonbuk 565-701, Republic of Korea.
authors.forename: Mun Yhung
authors.initials: MY
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, Gyeongnam 660-702, Republic of Korea.
authors.forename: Hye Song
authors.initials: HS
authors.lastname: Lim
authors.affiliation: Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, Gyeongnam 660-702, Republic of Korea.
authors.forename: Min-Gyu
authors.initials: MG
authors.lastname: Jeon
authors.affiliation: Department of Internal Medicine, Gyeongsang National University College of Medicine, Jinju, Gyeongnam 660-702, Republic of Korea. Electronic address: goldgu@gnu.ac.kr.
authors.forename: Sang-Il
authors.initials: SI
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea. Electronic address: bhpark@jbnu.ac.kr.
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000378:metabolism / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000178:diet therapy / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004042:Dietary Fats, Unsaturated / Q000378:metabolism / Q000627:therapeutic use; D019587:Dietary Supplements; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000378:metabolism* / Q000627:therapeutic use; D043371:Fatty Acids, Omega-6 / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008822:Mice, Transgenic; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D018501:Antirheumatic Agents; D029742:Caenorhabditis elegans Proteins; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D015850:Interleukin-6; D011994:Recombinant Proteins; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; C466741:fat-1 protein, C elegans; C577686:interleukin-6, mouse; D044943:Fatty Acid Desaturases
keywords: IL-6; K/BxN; RA; fat-1; n-3 PUFA