Analysis of mechanisms of rheumatoid arthritis associated with obesity

• Project/Area Number: 26670479
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Collagenous pathology/Allergology
• Research Institution: Tokyo Medical University
• Principal Investigator: Fujita Hidetoshi 東京医科大学, 医学部, 講師 (90571802)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000); Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: リウマチ / 肥満 / シノビオリン / 阻害剤 / 脂肪 / 小胞体ストレス

Outline of Final Research Achievements

Obesity was related to the increase of risk of the rheumatic onset. However, the molecular mechanism is not clear. We demonstrated that synoviolin (SYVN1) was important in rheumatoid arthritis (RA) and obesity. We showed that SYVN1 was causing factor of RA and SYVN1 inhibitor repressed RA in collagen-induced arthritis mice model. We recently demonstrated that Syvn1 knockoutl mice was associated with weight loss and reduced white adipose tissue abundance. In this study, we investigated the expression of SYVN1 in the obesity. SYVN1 was highly expressed in the obese mice (ob/ob and db/db mice) and obese human. We next examined the effects of SYVN1 inhibitor. SYVN1 inhibitors prevented age-related weight gain in wild-type mice and obese mice. In addition, reduction of white adipose tissue was observed. We found inhibitory effects of SYVN1 in natural products. Our findings indicate the potential usefulness of SYVN1 inhibitor in preventing and treating obesity and RA.

Research Products

• [Journal Article] Mitochondrial Ubiquitin Ligase Activator of NF-κB (MULAN) regulates NF-κB signaling in ER stress-stimulated cells. (2016)
  • Author(s): Fujita H, Aratani S, Fujii R, Yamano Y, Yagishita N, Araya N, Izumi T, Azakami K, Hasegawa D, Nishioka K and Nakajima T
  • Journal Title: Int J Mol Med. Volume: 37 Issue: 6 Pages: 1611-1618
  • DOI: 10.3892/ijmm.2016.2566
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] The E3 ligase synoviolin controls body weight and mitochondrial biogenesis through negative regulation of PGC-1β. (2015)
  • Author(s): Fujita H, Yagishita N, Aratani S, Saito-Fujita T, Morota S, Yamano Y, Hansson MJ, Inazu M, Kokuba H, Sudo K, Sato E, Kawahara K, Nakajima F, Hasegawa D, Higuchi I, Sato T, Araya N, Usui C, Nishioka K, Nakatani Y, Maruyama I, Usui M, Hara N, Uchino H, Elmer E, Nishioka K, Nakajima T.
  • Journal Title: EMBO J. Volume: 34 Issue: 8 Pages: 1042-55
  • DOI: 10.15252/embj.201489897
  • Peer Reviewed / Open Access
• [Presentation] 慢性炎症に関わるシノビオリンの新規エネルギー代謝調節機構 (2015)
  • Author(s): 藤田英俊、荒谷聡子、八木下尚子、須藤カツ子、中島若巳、内野博之、西岡久寿樹、中島利博
  • Organizer: BMB2015 (第38回 日本分子生物学会年会、第88回日本生化学会大会 合同大会）
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2015-12-03
• [Presentation] 慢性炎症に関わるシノビオリンの新しい生体機能 (2015)
  • Author(s): 藤田 英俊、荒谷聡子、八木下尚子、西岡久寿樹、中島利博
  • Organizer: 日本線維筋痛症学会第7回学術集会
  • Place of Presentation: ベルサール新宿
  • Year and Date: 2015-10-03
  • Invited
• [Presentation] 慢性炎症に機能するシノビオリンの新しい生体機能 (2015)
  • Author(s): 藤田英俊
  • Organizer: 第 16回 運動器科学研究会
  • Place of Presentation: 南日本新聞社 みなみホール、鹿児島
  • Year and Date: 2015-09-11
• [Presentation] 慢性炎症と肥満とをつなぐシノビリオンにおるエネルギー代謝調節機構 (2015)
  • Author(s): 藤田英俊、荒谷聡子、中島利博、須藤カツ子、中島若巳、稲津正人、西岡久寿樹、原直美、内野博之
  • Organizer: 第175回東京医科大学医学会総会
  • Place of Presentation: 東京医科大学
  • Year and Date: 2015-06-06
• [Presentation] リウマチ発症因子シノビオリンによるエネルギー代謝調節機構 (2014)
  • Author(s): 藤田英俊、荒谷聡子、中島利博、中島若巳、西岡久寿樹、諸田沙織、内野博之、須藤カツ子
  • Organizer: 第174回東京医科大学医学会総会
  • Place of Presentation: 東京医大（東京）
  • Year and Date: 2014-11-01
• [Presentation] リウマチ発症因子シノビオリンによる新規エネルギー代謝調節機構 (2014)
  • Author(s): 藤田英俊
  • Organizer: 第15回運動器科学研究会
  • Place of Presentation: ベルサール三田（東京）
  • Year and Date: 2014-09-04 – 2014-09-05
• [Presentation] E3ユビキチンリガーセであるシノビオリンによる体重制御機構 (2014)
  • Author(s): 藤田英俊、荒谷聡子、八木下尚子、西岡久寿樹、中島利博
  • Organizer: 第58回日本リウマチ学会
  • Place of Presentation: グランドプリンスホテル新高輪（東京）
  • Year and Date: 2014-04-26