Elucidation of sPLA2 network as a regulator of metabolic inflammation

• Project/Area Number: 25860059
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: SATO Hiroyasu 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 研究員 (50546629)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 分泌性ホスホリパーゼ / メタボリックシンドローム / 慢性炎症 / 脂質代謝 / 分泌性ホスホリパーゼA2

Outline of Final Research Achievements

To elucidate the role of secreted phospholipase A2 (sPLA2) in metabolic syndrome, we analyzed high fat diet-fed mice knockout mice for individual sPLA2 isoforms. We found that (1) sPLA2-IIE altered minor lipoprotein phospholipids, phosphatidylserine (PS) and phosphatidylethanolamine (PE), and moderately facilitated lipid accumulation in adipose tissue and liver. (2) sPLA2-IID plays a role in amelioration of metabolic syndrome. (3) sPLA2-III facilitated recruitment of immune cells such as mast cells in adipose tissue. (4) sPLA2-X plays a role in amelioration of metabolic syndrome.

Research Products

• [Journal Article] The adipocyte-inducible secreted phospholipases PLA2G5 and PLA2G2E play distinct roles in obesity. (2014)
  • Author(s): Sato H, Taketomi Y, Ushida A, Isogai Y, Kojima T, Hirabayashi T, Miki Y, Yamamoto K, Nishito Y, Kobayashi T, Ikeda K, Taguchi R, Hara S, Ida S, Miyamoto Y, Watanabe M, Baba H, Miyata K, Oike Y, Gelb MH, Murakami M.
  • Journal Title: Cell Metab. Volume: 20 Issue: 1 Pages: 119-132
  • DOI: 10.1016/j.cmet.2014.05.002
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Emerging roles of secreted phospholipase A2 enzymes: the 3rd edition. (2014)
  • Author(s): Murakami M, Taketomi Y, Miki Y, Sato H, Yamamoto K, Lambeau G.
  • Journal Title: Biochimie Volume: 107Pt A Pages: 105-113
  • DOI: 10.1016/j.biochi.2014.09.003
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] ホスホリパーゼA2による脂質代謝シグナル制御. (2014)
  • Author(s): 佐藤弘泰, 村上誠
  • Journal Title: 実験医学 Volume: 32 (15) Pages: 2359-2365
• [Journal Article] Oligo-astheno-teratozoospermia in mice lacking ORP4, a sterol-binding protein in the OSBP-related protein family. (2014)
  • Author(s): Udagawa O, Ito C, Ogonuki N, Sato H, Lee S, Tripvanuntakul P, Ichi I, Uchida Y, Nishimura T, Murakami M, Ogura A, Inoue T, Toshimori K, Arai H.
  • Journal Title: Genes Cells. Volume: 19 Issue: 1 Pages: 13-27
  • DOI: 10.1111/gtc.12105
  • Peer Reviewed
• [Journal Article] Lymphoid tissue phospholipase A2 group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators. (2013)
  • Author(s): Miki Y, Yamamoto K, Taketomi Y, Sato H, Shimo K, Kobayashi T, Ishikawa Y, Ishii T, Nakanishi H, Ikeda K, Taguchi R, Kabashima K, Arita M, Arai H, Lambeau G, Bollinger JM, Hara S, Gelb MH, Murakami M.
  • Journal Title: J Exp Med. Volume: 210 Issue: 6 Pages: 1217-1234
  • DOI: 10.1084/jem.20121887
  • Peer Reviewed
• [Journal Article] Mast cell maturation is driven via a novel group III phospholipase A2-prostaglandin D2-DP1 receptor paracrine axis. (2013)
  • Author(s): Taketomi, Y., Morimoto, K., Murakami, M., et al., 他30名
  • Journal Title: Nature Immunol. Volume: (印刷中) Issue: 6 Pages: 554-63
  • DOI: 10.1038/ni.2586
  • Peer Reviewed
• [Presentation] メタボリックシンドロームにおける分泌性ホスホリパーゼA2受容体の機能. (2015)
  • Author(s): 池田さや, 佐藤弘泰, 武富芳隆, 田中弘文, 村上誠
  • Organizer: 日本薬学会第135年会
  • Place of Presentation: 神戸学院大学 (神戸)
  • Year and Date: 2015-03-26 – 2015-03-28
• [Presentation] Deficiency of group III sPLA2 protects from metabolic disorders. (2015)
  • Author(s): Sato, H., Taketomi, Y., Yamamoto, K., Hara, S., Murakmai, M.
  • Organizer: PLM2015
  • Place of Presentation: 京王プラザホテル (東京)
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] Deficiency of group III sPLA2 protects from atherosclerosis. (2015)
  • Author(s): Taketomi, Y., Miyazaki, T., Sato, H., Murakami, M.
  • Organizer: PLM2015
  • Place of Presentation: 京王プラザホテル (東京)
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] Group X sPLA2 protects from colitis by mobilizing ω3 polyunsaturated fatty acid metabolites. (2015)
  • Author(s): Murase, R., Taketomi, Y., Sato, H., Yamamoto, K., Tamamoto, T., Murakami, M.
  • Organizer: PLM2015
  • Place of Presentation: 京王プラザホテル (東京)
  • Year and Date: 2015-02-10 – 2015-02-12
• [Presentation] Adipocyte-inducible group V and IIE sPLA2s play distinct roles in metabolic disorders. (2015)
  • Author(s): Sato, H., Taketomi, Y., Yamamoto, K., Hara, S., Miyata, K., Oike, Y., Gelb, M.H., Murakami, M.
  • Organizer: PLM2015
  • Place of Presentation: 京王プラザホテル (東京)
  • Year and Date: 2015-02-10
• [Presentation] V型分泌性ホスホリパーゼA2は「Th2/M2-prone sPLA2」である． (2014)
  • Author(s): 佐藤弘泰，武富芳隆，池田さや，村上誠
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 国立京都国際会館 (京都)
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 炎症性腸疾患における分泌性ホスホリパーゼA2の機能解析. (2014)
  • Author(s): 村瀬礼美，武富芳隆，佐藤弘泰，山本圭，山元俊憲，村上誠
  • Organizer: 第87回日本生化学会
  • Place of Presentation: 国立京都国際会館 (京都)
  • Year and Date: 2014-10-15 – 2014-10-18
• [Presentation] 代謝性慢性炎症を制御するメタボリックsPLA2. (2014)
  • Author(s): 佐藤弘泰, 村上誠
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館 (沖縄)
  • Year and Date: 2014-07-01 – 2014-07-04
  • Invited
• [Presentation] III型分泌性ホスホリパーゼA2はメタボリックシンドロームを制御する. (2014)
  • Author(s): 佐藤弘泰, 武富芳隆, 山本圭, 原俊太郎, 村上誠
  • Organizer: 第35回日本炎症・再生医学会
  • Place of Presentation: 万国津梁館 (沖縄)
  • Year and Date: 2014-07-01 – 2014-07-04
• [Presentation] Phospholipase A2 and Lipid Mediators in Health and Disease. (2014)
  • Author(s): Murakami, M., Taketomi, Y., Sato, H., Miki, Y., Yamamoto, K.
  • Organizer: 医学研・延世大学Joint Symposium，Yonsei・CBSM Joint Conference
  • Place of Presentation: ソウル (韓国)
  • Year and Date: 2014-06-19 – 2014-06-22
• [Presentation] III型分泌性ホスホリパーゼA2はメタボリックシンドロームを制御する (2014)
  • Author(s): 佐藤弘泰, 武富芳隆, 牛田絢子, 山本圭, 小島卓巳, 原俊太郎, 村上誠
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] III型分泌性ホスホリパーゼA2は動脈硬化を制御する (2014)
  • Author(s): 武富芳隆, 宮崎拓郎, 佐藤弘泰, 村上誠
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
• [Presentation] sPLA2と免疫抑制 (2014)
  • Author(s): 村上誠, 三木寿美, 佐藤弘泰, 武富芳隆
  • Organizer: 日本薬学会第134年会
  • Place of Presentation: 熊本
  • Invited
• [Presentation] Two secreted phospholipase A2 enzyme, PLA2G5 and PLA2G2E, are induced in hypertrophic adipocytes and distinctly regulate obesity. (2013)
  • Author(s): Sato H, Taketomi Y, Ushida A, Yamamoto K, Gelb M. H, Murakami M.
  • Organizer: 13h International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases
  • Place of Presentation: San Juan, Puerto Rico.
• [Presentation] 脂質メディエーターの観点から捉えた慢性炎症と肥満症． (2013)
  • Author(s): 村上誠，佐藤弘泰，武富芳隆
  • Organizer: 第34回日本肥満学会
  • Place of Presentation: 東京
  • Invited
• [Presentation] III型分泌性ホスホリパーゼA2の欠損はメタボリックシンドロームを改善する. (2013)
  • Author(s): 佐藤弘泰, 武富芳隆, 牛田絢子, 山本圭, 小島卓巳, 原俊太郎, 村上誠
  • Organizer: 第86回日本生化学会
  • Place of Presentation: 横浜
• [Presentation] 生体膜リン脂質研究の最前線． (2013)
  • Author(s): 村上誠，武富芳隆，佐藤弘泰，三木寿美，山本圭
  • Organizer: 第86回日本生化学会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] III型分泌性ホスホリパーゼA2は動脈硬化を制御する． (2013)
  • Author(s): 武富芳隆, 宮崎拓郎, 佐藤弘泰, 村上誠
  • Organizer: 第86回日本生化学会
  • Place of Presentation: 横浜
• [Presentation] 炎症性腸疾患における分泌性ホスホリパーゼA2の機能解析． (2013)
  • Author(s): 村瀬礼美, 武富芳隆, 佐藤弘泰, 三木寿美, 山本圭, 山元俊憲, 村上誠
  • Organizer: 第86回日本生化学会
  • Place of Presentation: 横浜
• [Presentation] 脂肪過栄養により誘導されるsPLA2-VとsPLA2-IIEは全身性脂質代謝を制御する． (2013)
  • Author(s): 佐藤弘泰, 武富芳隆, 牛田絢子, 小島卓巳, 山本圭, 原俊太郎, 宮田敬士, 尾池雄一, 村上誠
  • Organizer: 第55回日本脂質生化学会
  • Place of Presentation: 松島
• [Presentation] Group III phospholipase A2 regulates mast cell maturation and anaphylaxis through a novel paracrine PGD2 loop. (2013)
  • Author(s): Taketomi Y, Ueno N, Sato H, Yamamoto K, Murakami M.
  • Organizer: 5th International Conference on Phospholipase A2 Mediated Signaling in Translational Medicine.
  • Place of Presentation: New Orleans, LA, USA.
• [Presentation] 脂肪過栄養により誘導されるsPLA2-VとsPLA2-IIEは全身性脂質代謝を制御する
  • Author(s): 佐藤弘泰, 武富芳隆, 牛田絢子, 山本圭, 宮田敬士, 尾池雄一, 村上誠
  • Organizer: 第8回炎症・脂質代謝・メタボリサーチフォーラム
  • Place of Presentation: 東京
• [Remarks] World Biomedical Frontiers
  • URL: http://biomedfrontiers.org/diabetes-obesity-2014-12-1/
• [Remarks] 脂肪細胞から分泌されるリン脂質分解酵素PLA2G5とPLA2G2Eは肥満において異なる役割を担う
  • URL: http://first.lifesciencedb.jp/archives/8936#more-8936
• [Remarks] 脂肪細胞から分泌される脂質代謝酵素による肥満の新しい調節機構の発見．
  • URL: http://www.metro.tokyo.jp/INET/OSHIRASE/2014/06/20o69200.htm
• [Remarks] 東京都医学総合研究所 脂質代謝プロジェクト
  • URL: http://www.igakuken.or.jp/lipid/