New paradigm for secreted phospholipase A2 to control lipid metabolism and obesity.

• Project/Area Number: 23790120
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Biological pharmacy
• Research Institution: 公益財団法人東京都医学総合研究所 (2012); Tokyo Metropolitan Organization for Medical Research (2011)
• 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): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: メタボリックシンドローム / ホスホリパーゼA2 / リポタンパク質 / リン脂質 / 脂質

Research Abstract

Metabolic disorders including obesity and insulin resistance have their basis on dysregulated lipid metabolism and low-grade inflammation. In a microarray search of unique lipase-related genes whose expressions are associated with obesity, we found that two secreted phospholipase A_2 (sPLA_2) enzymes, PLA2G5 and PLA2G2E, were robustly induced in adipocytes of obese mice. Analyses of Pla2g5^<-/-> and Pla2g2e^<-/-> mice revealed distinct and previously unrecognized roles of these sPLA_2s in diet-induced obesity. PLA2G5 protects from obesity-associated metabolic disorders by normalizing phosphatidylcholine in fat-overladen low-density lipoprotein and by tipping the immune balance toward a Th2-M2 state that counteracts adipose tissue inflammation. Collectively, the identification of “metabolic sPLA_2s” adds this gene family to a growing list of lipolytic enzymes that act as metabolic coordinators.

Research Products

• [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
  • 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
• [Journal Article] AMP-activated protein kinase negatively regulates FcεRI-mediated mast cell signaling and anaphylaxis in mice. (2013)
  • Author(s): Hwang SL, Li X, Lu Y, Jin Y, Jeong YT, Kim YD, Lee IK, Taketomi Y, Sato H, Cho YS, Murakami M, Chang HW.
  • Journal Title: J Allergy Clin Immunol. Volume: 132 Issue: 3 Pages: 729-736
  • DOI: 10.1016/j.jaci.2013.02.018
  • Peer Reviewed
• [Journal Article] Hair follicular expression and function of group X secreted phospholipase A_2 in mouse skin (2011)
  • Author(s): Yamamoto, K., Taketomi, T., Isogai, Y., Miki, Y., Sato, H., Masuda, S., Nishito, Y., Morioka, K., Ishimoto, Y., Suzuki, N., Yokoya, Y., Hanasaki, K., Ishikawa, Y., Ishii, T., Kobayashi, T., Fukami, K., Ikeda, K., Nakanishi, H., Taguchi, R., and Murakami, M.
  • Journal Title: J. Biol. Chem Volume: 286 Issue: 13 Pages: 11616-11631
  • DOI: 10.1074/jbc.m110.206714
  • Peer Reviewed
• [Journal Article] Physiological roles of group X secreted phospholipase A_2 in reproduction, gastrointestinal phospholipid digestion, and neuronal function (2011)
  • Author(s): Sato, H., Isogai, Y., Masuda, S., Taketomi, Y., Miki, Y., Kamei, D., Hara, S., Kobayashi, T., Ishikawa, Y., Ishii, T., Ikeda, K., Taguchi, R., Ishimoto, Y., Suzuki, N., Yokota, Y., Hanasaki, K., Suzuki-Yamamoto, T., Yamamoto, K., and Murakami, M.
  • Journal Title: J. Biol. Chem Volume: 286 Issue: 13 Pages: 11632-11648
  • DOI: 10.1074/jbc.m110.206755
  • Peer Reviewed
• [Journal Article] Recent progress in phospholipase A_2 research : from cells to animals to humans (2011)
  • Author(s): Murakami, M., Taketomi, Y., Miki, Y., Sato, H., Hirabayashi, T., and Yamamoto, K.
  • Journal Title: Prog. Lipid Res Volume: 50 Issue: 2 Pages: 152-192
  • DOI: 10.1016/j.plipres.2010.12.001
  • Peer Reviewed
• [Journal Article] Secreted phospholipase A_2, lipoprotein hydrolysis, and atherosclerosis : integration with lipidomics (2011)
  • Author(s): Yamamoto, K., et al
  • Journal Title: Anal.Bioanal.Chem. Volume: 400 Issue: 7 Pages: 1829-1842
  • DOI: 10.1007/s00216-011-4864-z
  • Peer Reviewed
• [Journal Article] Integrated lipidomics in the secreted phospholipase A2 biology. (2011)
  • Author(s): Murakami M, Sato H, Taketomi Y, Yamamoto K.
  • Journal Title: Int J Mol Sci. Volume: 12 Pages: 1474-1495
  • Peer Reviewed
• [Journal Article] Secreted phospholipase A_2 revisited (2011)
  • Author(s): Murakami, M., Taketomi, Y., Sato, H., and Yamamoto, K.
  • Journal Title: J. Biochem. Volume: 150 Issue: 3 Pages: 233-255
  • DOI: 10.1093/jb/mvr088
  • NAID: 10030587186
  • Peer Reviewed
• [Presentation] メタボリックシンドロームにおけるX型分泌型ホスホリパーゼA_2の役割 (2012)
  • Author(s): 佐藤弘泰, 武富芳隆, 山本圭, 小島卓巳, 原俊太郎, 村上誠
  • Organizer: 第85回日本生化学会大会, 【鈴木紘一メモリアル賞(優秀プレゼンテーション賞)受賞】
  • Place of Presentation: 福岡
• [Presentation] メタボリックシンドロームにおけるIID型、IIE型分泌型ホスホリパーゼA_2の役割 (2012)
  • Author(s): 牛田絢子, 佐藤弘泰, 武富芳隆, 山本圭, 小島卓巳, 三木寿美, 小林哲幸, 村上誠
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] マスト細胞を制御するホスホリパーゼA_2分子群の網羅的解析 (2012)
  • Author(s): 上野紀子, 武富芳隆, 小島卓巳, 田中智之, 依田恵美子, 佐藤弘泰, 平林哲也, 山本圭, 原俊太郎, 村上誠
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] 皮膚病態生理機能におけるIIE型分泌性ホスホリパーゼA_2の役割 (2012)
  • Author(s): 山本圭, 佐藤弘泰, 佐藤真利子, 三木寿美, 武富芳隆, 村上誠
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] PLA2G5, a sectered phospholipase A_2 induced in hypertrophic adipocytes, regulates systemic lipid metabolism and obesity (2012)
  • Author(s): Sato H, Taketomi Y, Kojima T, Ushida A, Yamamoto K, Ikeda K, Hara S, Miyata K, Oike Y, Murakami M
  • Organizer: IEIIS2012
  • Place of Presentation: Tokyo, Japan
• [Presentation] PLA2G3, a mammalian homolog of anaphylactic sectered phospholipase A_2 in bee venom, facilitates proper maturation of mast cells through the paracrine PGD_2 loop (2012)
  • Author(s): Taketomi Y, Ueno N, Kojima T, Tanaka S, Sato H, Nishito Y, Yamamoto K, Sugimoto Y, Hara S, Murakami M
  • Organizer: The 12^<th> Annual International Endotoxin & Innate Immunity Society (IEIIS) Meeting
  • Place of Presentation: Tokyo, Japan
• [Presentation] マスト細胞を制御する新しい脂質マシナリー (2012)
  • Author(s): 武富芳隆, 上野紀子, 小島卓巳, 田中智之, 佐藤弘泰, 山本圭, 有竹浩介, 裏出良博, 杉本幸彦, 成宮周, 原俊太郎, 村上誠
  • Organizer: 第33回日本炎症・再生医学会
  • Place of Presentation: 福岡
• [Presentation] マスト細胞を制御する新しい脂質マシナリー (2012)
  • Author(s): 武富芳隆, 上野紀子, 小島卓巳, 田中智之, 佐藤弘泰, 西藤泰昌, 山本圭, 有竹浩介, 裏出良博, 杉本幸彦, 成宮周, 原俊太郎, 村上誠
  • Organizer: 第54回脂質生化学会
  • Place of Presentation: 福岡
• [Presentation] sPLA_2とメタボリックシンドローム (2012)
  • Author(s): 佐藤弘泰 武富芳隆, 山本圭, 池田和貴, Arm, J.P., 村上誠
  • Organizer: 新学術領域領域「生命応答を制御する脂質マシナリー」若手ワークショップ
  • Place of Presentation: 東京
• [Presentation] sPLA_2とアナフィラキシー (2012)
  • Author(s): 武富芳隆, 小島卓巳, 上野紀子, 佐藤弘泰, 山本圭, 有竹浩介, 裏出良博, 杉本幸彦, 成宮周, 原俊太郎, 村上誠
  • Organizer: 新学術領域領域「生命応答を制御する脂質マシナリー」若手ワークショップ
  • Place of Presentation: 東京
• [Presentation] Secreted phospholipase A_2s in metabolic syndrome (2011)
  • Author(s): Sato, H., Taketomi, Y., Yamamoto, K., Ikeda, K., Arm, J.P., Murakami, M
  • Organizer: 第10回JBSバイオフロンティア国際シンポジウム New Aspects of Phospholipid Biology and Medicine 2011
  • Place of Presentation: 福岡
• [Presentation] Secreted phospholipase A_2s in male reproduction (2011)
  • Author(s): Ushida, A., Sato, H., Yamamoto, K., Ikeda, K., Kobayashi T., Murakami, M
  • Organizer: 第10回JBSバイオフロンティア国際シンポジウム New Aspects of Phospholipid Biology and Medicine 2011
  • Place of Presentation: 福岡
• [Presentation] Secreted phospholipase A_2s in anaphylaxis (2011)
  • Author(s): Taketomi, Y., Kojima, T., Ueno, N., Sato, H., Yamamoto, K., Aritake, K., Urade, Y., Sugimoto, Y., Narimiya, S., Murakami, M
  • Organizer: 第10回JBSバイオフロンティア国際シンポジウム New Aspects of Phospholipid Biology and Medicine 2011
  • Place of Presentation: 福岡
• [Presentation] Hair follicular expression and function of group X secreted phospholipase A_2 in mouse skin (2011)
  • Author(s): Yamamoto, K., Taketomi, Y., Miki, Y., Sato, H., Ikeda, K., Nakanishi, H., Taguchi, R., Murakami, M
  • Organizer: The 8~<th> GERLI Lipidomics meeting
  • Place of Presentation: Lyon, France
• [Presentation] X型分泌性ホスホリパーゼA_2の消化、神経機能、体毛形成における新規機能 (2011)
  • Author(s): 佐藤弘泰, 武富芳隆, 池田和貴, 田口良, 山本登志子, 山本圭, 村上誠
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] X型分泌性ホスホリパーゼA_2の生殖における新規機能 (2011)
  • Author(s): 牛田絢子, 佐藤弘泰, 池田和貴, 山本圭, 小林哲幸, 村上誠
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Getting new insights into the functions of sPLA_2s (2011)
  • Author(s): Murakami, M., Sato, H., Taketomi, Y., Yamamoto, K
  • Organizer: 12^<th> International conference "Bioactive lipids in cancer, inflammation, and related diseases"
  • Place of Presentation: Seattle, Washington, USA
• [Presentation] Deregnaucourt, C., Ninio, E., Karabina, S., Muramaki, M.:Biology of group X secreted phospholipase A_2: from physiology to cancer and inflammatory diseases (2011)
  • Author(s): Lambeau, G., Jemel, I., Escoffier, J., Ait-Oufella, H., Li, H., Guillaume, C., Gora, S., Surrel, F., Coatrieux, C., Payre, C., Tanemoto, A., Taketomi, Y., Sato, H., Yamamoto, K., Arnoult, C., Mallat, Z., Gelb, M. H
  • Organizer: 12^<th> International conference "Bioactive lipids in cancer, inflammation, and related diseases"
  • Place of Presentation: Seattle, Washington, USA
• [Presentation] An adipokine-like phospholipase A_2 from hypertrophied adipocytes controls lipid metabolism and obesity (2011)
  • Author(s): Sato, H., Taketomi, Y., Ikeda, K., Arm, J. P., Murakami, M
  • Organizer: 12^<th> International conference "Bioactive lipids in cancer, inflammation, and related diseases"
  • Place of Presentation: Seattle, Washington, USA
• [Presentation] Roles of multiple sPLA_2 enzymes in obesity, hepatic steatosis, insulin tolerance, lipoprotein metabolism and adipose inflammation (2011)
  • Author(s): Sato, H., Taketomi, Y., Yamamoto, K., Murakami, M
  • Organizer: The 30^<th> Naito conference on membrane dynamics and lipid biology [II]: domeins, droplets and diseases
  • Place of Presentation: 札幌
• [Presentation] 外根鞘に局在するsPLA_2-Xは体毛の恒常性維持に関与する (2011)
  • Author(s): 山本圭, 武富芳隆, 三木寿美, 佐藤弘泰, 池田和貴, 中西広樹, 田口良, 村上誠
  • Organizer: 第53回日本脂質生化学会
  • Place of Presentation: 東京
• [Presentation] 脂肪過栄養により誘導されるsPLA_2-Vは全身的な脂質代謝異常を制御する (2011)
  • Author(s): 佐藤弘泰, 武富芳隆, 山本圭, 磯貝有紀, 石川由紀雄, 石井壽晴, 原俊太郎,村上誠
  • Organizer: 第53回日本脂質生化学会
  • Place of Presentation: 東京
• [Presentation] Roles of multiple sPLA2 enzymes in obesity, hepatic steatosis, insulin tolerance, lipoprotein metabolism and adipose inflammation. (2011)
  • Author(s): Sato H, Taketomi Y, Yamamoto K, and Murakami M
  • Organizer: The 30th Naito conference on membrane dynamics and lipid biology [II]: domeins, droplets and diseases.
  • Place of Presentation: 北海道
• [Presentation] An Adipokine-like Phospholipase A2 from Hypertrophied Adipocytes Controls Lipid Metabolism and Obesity. (2011)
  • Author(s): Sato H, Taketomi Y, Kazutaka I, Arm JP and Murakami M.
  • Organizer: 12th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases
  • Place of Presentation: Seattle, USA
• [Presentation] Getting new insights into the functions of sPLA2s (2011)
  • Author(s): Murakami M, Sato H, Taketomi Y, Yamamoto K.
  • Organizer: 12th International Conference on Bioactive Lipids in Cancer, Inflammation, and Related Diseases
  • Place of Presentation: Seattle, USA
• [Presentation] Hair follicular expression and function of group X secreted phospholipase A2 in mouse skin (2011)
  • Author(s): Yamamoto K, Taketomi Y, Miki Y, Sato H, Ikeda K, Nakanishi H, Taguchi R, Murakami M.
  • Organizer: The 8th GERLI Lipidomics meeting
  • Place of Presentation: Lyon, France
• [Presentation] SECRETED PHOSPHOLIPASE A2S IN METABOLIC SYNDROME (2011)
  • Author(s): Sato H, Taketomi Y, Yamamoto K, Ikeda K, Arm JP, Murakami M.
  • Organizer: 第10回JBSバイオフロンティア国際シンポジウム
  • Place of Presentation: 福岡
• [Presentation] SECRETED PHOSPHOLIPASE A2S IN MALE REPRODUCTION (2011)
  • Author(s): Ushida A, Sato H, Yamamoto K, Ikeda K, Kobayashi T, Murakami M.
  • Organizer: 第10回JBSバイオフロンティア国際シンポジウム
  • Place of Presentation: 福岡
• [Presentation] SECRETED PHOSPHOLIPASE A2S IN ANAPHYLAXIS (2011)
  • Author(s): Taketomi Y, Kojima T, Ueno N, Sato H, Yamamoto K, Aritake K, Urade Y, Sugimoto Y, Narimiya S, Murakami M.
  • Organizer: 第10回JBSバイオフロンティア国際シンポジウム
  • Place of Presentation: 福岡
• [Presentation] 脂肪過栄養により誘導されるsPLA2-Vは全身的な脂質代謝異常を制御する (2011)
  • Author(s): 佐藤弘泰, 武富芳隆, 山本圭, 磯貝有紀, 石川由 紀雄, 石井壽晴, 原俊太郎, 村上誠
  • Organizer: 第53回日本脂質生化学会
  • Place of Presentation: 東京
• [Presentation] 外根鞘に局在するsPLA2-Xは体毛の恒常性維持に関与する (2011)
  • Author(s): 山本圭, 武富芳隆, 三木寿美, 佐藤弘泰, 池田和 貴, 中西広樹, 田口良, 村上誠
  • Organizer: 第53回日本脂質生化学会
  • Place of Presentation: 東京
• [Presentation] X型分泌性ホスホリパーゼA2の消化、神経機能、体毛形成における新規機能 (2011)
  • Author(s): 佐藤弘泰, 武富芳隆, 池田和貴, 田口良, 山本登 志子, 山本圭, 村上誠
  • Organizer: 第84回日本生化学会大会
  • Place of Presentation: 京都
• [Presentation] Murakami M. PLA2G5, a sectered phospholipase A2 induced in hypertrophic adipocytes, regulates systemic lipid metabolism and obesity.
  • Author(s): Sato H, Taketomi Y, Kojima T, Ushida A, Yamamoto K, Ikeda K, Hara S, Miyata K, Oike Y, Murakami M.
  • Organizer: IEIIS2012
  • Place of Presentation: 東京
• [Presentation] メタボリックシンドロームにおけるX型分泌型ホスホリパーゼA2の役割
  • Author(s): 佐藤弘泰, 武富芳隆, 山本圭, 小島卓巳, 原俊太郎, 村上誠
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] メタボリックシンドロームにおけるIID型、IIE型分泌型ホスホリパーゼA2の役割
  • Author(s): 牛田絢子, 佐藤弘泰, 武富芳隆, 山本圭, 小島卓巳, 三木寿美, 小林哲幸, 村上誠
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] マスト細胞を制御するホスホリパーゼA2分子群の網羅的解析
  • Author(s): 上野紀子, 武富芳隆, 小島卓巳, 田中智之, 依田恵美子, 佐藤弘泰, 平林哲也, 山本圭, 原俊太郎, 村上誠
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Presentation] 皮膚病態生理機能におけるIIE型分泌性ホスホリパーゼA2の役割
  • Author(s): 山本圭, 佐藤弘泰, 佐藤真利子, 三木寿美, 武富芳隆, 村上誠
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡
• [Book] 生命科学研究の戦略：疾患モデルマウスと表現型解析 (2011)
  • Author(s): 佐藤弘泰, 武富芳隆, 山本圭, 村上誠
  • Total Pages: 10
  • Publisher: 中山書店
• [Remarks]
  • URL: http://www.igakuken.or.jp/
• [Remarks] 東京都医学総合研究所 脂質代謝プロジェクト (村上研究室)
  • URL: http://www.igakuken.or.jp/lipid/index_japanese.html