Obesity-induced activation of cytokine-producing cells and eosinophils in adipose tissues.

• Project/Area Number: 17KT0132
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 特設分野
• Research Field: Complex Systems Disease Theory
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Takaki Satoshi 国立研究開発法人国立国際医療研究センター, その他部局等, 免疫制御研究部長 (10242116)
• Project Period (FY): 2017-07-18 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 脂肪組織 / 肥満 / サイトカイン / 好酸球 / アレルギー

Outline of Final Research Achievements

Obesity-induced adipose tissue inflammation is now recognized to have critical roles in the development of metabolic diseases. Recently it has been shown that NK/ILC1s in adipose tissues are activated in early stage of inflammation in response to high fat diet (HFD). Mice fed with HFD mainly composed of unsaturated fatty acids showed significant obesity compared to those fed with HFD mainly composed of saturated fatty acids. We then investigated changes in adipose in early stage of HFD feeding. Mice fed by HFD with unsaturated fatty acids showed increased IFN+ NK1.1+ cells in adipose tissues by 1 week after HFD start. We found that products of lipid peroxidation derived from unsaturated fatty acids were significantly increased in adipose tissues. We prepared membrane fractions of adipose tissues cultured in the presence of products of lipid peroxidation, and found that the membranes induced more IFN+ NK1.1+ cells compared to membranes from adipose tissues cultured with medium alone.

Academic Significance and Societal Importance of the Research Achievements

本研究では、肥満に伴う脂肪炎症の発生機構、それに引き続く脂肪組織や肺の好酸球動態およびその制御機構を解析した。社会的にも問題となっているアレルギーやメタボリックシンドロームの制御に有用な知見収集を目指した。不飽和脂肪酸摂取により、内蔵脂肪内NK細胞群の増加とIFNγ産生がより活性化することを見出し、脂肪細胞の変化および修飾による脂肪炎症の初動機構理解に役立つものである。

Research Products

• [Int'l Joint Research] Konkuk Univ.(韓国)
• [Journal Article] The regulatory B cell?mediated peripheral tolerance maintained by mast cell IL-5 suppresses oxazolone-induced contact hypersensitivity (2019)
  • Author(s): Kim Hyuk Soon、Lee Min Bum、Lee Dajeong、Min Keun Young、Koo Jimo、Kim Hyun Woo、Park Young Hwan、Kim Su Jeong、Ikutani Masashi、Takaki Satoshi、Kim Young Mi、Choi Wahn Soo
  • Journal Title: Science Advances Volume: 5 Issue: 7
  • DOI: 10.1126/sciadv.aav8152
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cyclosporin A indirectly attenuates activation of group 2 innate lymphoid cells in papain-induced lung inflammation. (2018)
  • Author(s): Kudo F, Ikutani M, Iseki M, Takaki S.
  • Journal Title: Cell Immunology Volume: 323 Pages: 33-40
  • DOI: 10.1016/j.cellimm.2017.10.010
  • Peer Reviewed / Open Access
• [Presentation] Characterization of ILC2 in IL-33-induced chronic inflammation. (2018)
  • Author(s): Ikutani M, Tsuneyama K, Nakae S, Takatsu K, Takaki S.
  • Organizer: 第47回 日本免疫学会学術集会
• [Presentation] IL-5-producing ILC2s and eosinophils in the development of pulmonary arteriopathy. (2017)
  • Author(s): Takaki S.
  • Organizer: The 5th Annual Meeting of the International Cytokine and Interferon Society, Cytokines 2017.
  • Int'l Joint Research / Invited
• [Presentation] Chronic IL-33-induced inflammation results in pulmonary arterial hypertrophy. (2017)
  • Author(s): Ikutani M, Tsuneyama K, Nakae S, Takatsu K, Takaki S.
  • Organizer: 第46回 日本免疫学会学術集会