Molecular mechanism and biological significance of a novel intrinsic choline production pathway

• Project/Area Number: 15K15094
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: HIRABAYASHI Tetsuya 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, 主席研究員 (90345025)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: リン脂質代謝 / ホスファチジルコリン / コリン / メチオニン / メチル化 / メタボロミクス / 肝臓 / 神経変性 / グリセロホスホコリン

Outline of Final Research Achievements

We have found that the iPLA2gamma/iPLA2theta/GED axis functions as an intrinsic choline production pathway that mobilizes free choline from the membrane phospholipids in the liver and shown that this pathway is involved in the methionine regeneration and liver function. Moreover, iPLA2theta deficiency causes profound neuronal degeneration in the brain and browning of white adipose tissues, indicating that the novel choline production pathway that we have identified has also a crucial role in neuronal survival and energy metabolism.

Research Products

• [Journal Article] PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis. (2017)
  • Author(s): Hirabayashi T, Anjo T, Kaneko A, Senoo Y, Shibata A, Takama H, Yokoyama K, Nishito Y, Ono T, Taya C, Muramatsu K, Fukami K, Muñoz-Garcia A, Brash A, Ikeda K, Arita M, Akiyama M, Murakami M.
  • Journal Title: Nat Commun Volume: 8 Issue: 1 Pages: 14609-14609
  • DOI: 10.1038/ncomms14609
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 肝臓における新規ホスファチジルコリン分解経路の代謝恒常性における役割 (2016)
  • Author(s): 平林哲也、毛利美紗、徳岡涼美、北芳博、池田和貴、中田理恵子、村上誠
  • Organizer: 第89回日本生化学会大会
  • Place of Presentation: 仙台国際センター(宮城県仙台市)
  • Year and Date: 2016-09-25
• [Presentation] NPLA7-mediated catabolic pathway for phosphatidylcholine has a crucial role in hepatic choline metabolism and systemic energy homeostasis (2016)
  • Author(s): Tetsuya Hirabayashi, Misa Mouri, Suzumi M. Tokuoka, Yoshihiro Kita, Rieko Nakata, Kazutaka Ikeda and Makoto Murakami
  • Organizer: 7th International Conference on Phospholipase A2: From Bench To Translational Medicine
  • Place of Presentation: Scripps Seaside Forum (La Jolla, CA, 米国)
  • Year and Date: 2016-05-19
  • Int'l Joint Research
• [Presentation] 肝臓における新規グリセロホスホコリン産生経路 (2015)
  • Author(s): 平林哲也、毛利美紗、徳岡涼美、池田和貴、中田理恵子、北芳博、村上誠
  • Organizer: BMB2015
  • Place of Presentation: 神戸ポートアイランド（兵庫県神戸市）
  • Year and Date: 2015-12-01
• [Presentation] PNPLA7-mediated production of glycerophosphocholine from lysophosphatidylcholine has a pivotal role in hepatic choline metabolism and systemic energy homeostasis (2015)
  • Author(s): Tetsuya Hirabayashi, Misa Mouri, Toru Shimamura, Kazutaka Ikeda, Rieko Nakata, Makoto Murakami
  • Organizer: FASEB SRC Lysophospholipid and Related Mediators-from Bench to Clinic
  • Place of Presentation: Banff, Canada
  • Year and Date: 2015-08-24
  • Int'l Joint Research
• [Presentation] 肝臓コリン代謝における新規リン脂質代謝酵素PNPLA7の役割 (2015)
  • Author(s): 平林哲也、毛利美紗、三田村涼美、池田和貴、中田理恵子、北芳博、村上誠
  • Organizer: 第22回肝細胞研究会
  • Place of Presentation: 米子コンベンションセンター（鳥取県米子市）
  • Year and Date: 2015-06-04
• [Book] 「細胞内ホスホリパーゼA2」seriesモデル動物利用マニュアル 疾患モデルの作製と利用－脂質代謝異常と関連疾患 <下巻> (2015)
  • Author(s): 平林哲也、村上誠
  • Total Pages: 13
  • Publisher: エル・アイ・シー
• [Book] ホスホリパーゼA2と神経疾患、実験医学増刊 (2015)
  • Author(s): 平林哲也、村上誠
  • Total Pages: 6
  • Publisher: 羊土社
• [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/
• [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/home_j.html