Elucidation of phospholipid metabolism necessary for life

• Project/Area Number: 26870879
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Embryonic/Neonatal medicine; General medical chemistry
• Research Institution: National Center for Global Health and Medicine
• Principal Investigator: Yoshida Tomomi 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, その他 (30610216)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 発生医学 / 生体膜リン脂質

Outline of Final Research Achievements

This study demonstrated that LPCAT3, which is one of lysophospholipid acyltransferase, played a key role in biosynthesis of arachidonic acid containing phospholipids in vivo. LPCAT3-deficient mice showed a lethal phenotype within one week after birth. We also found that a triacylglycerol (TG) accumulation occurred by LPCAT3 deletion in small intestine at postnatal day 1. The study showed that an arachidonic acid containing phospholipid was important for an efficient TG transfer by an enzymatic assay in vitro. A glucose level and a TG level in blood were decreased in LPCAT3-deficient mice because enterocyte was disrupted by the accumulation. These results suggested that the dysfunction of enterocyte was one of the reasons for the neonatal lethal phenotype.

Research Products

• [Journal Article] Fatty acid remodeling by LPCAT3 enriches arachidonate in phospholipid membranes and regulates triglyceride transport. (2015)
  • Author(s): Hashidate-Yoshida T, Harayama T, Hishikawa D, Morimoto R, Hamano F, Tokuoka SM, Eto M, Tamura-Nakano M, Yanobu-Takanashi R, Mukumoto Y, Kiyonari H, Okamura T, Kita Y, Shindou H, Shimizu T.
  • Journal Title: Elife Volume: Apr 21;4 Pages: 4-4
  • DOI: 10.7554/elife.06328
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Essential Role of Lysophosphatidylcholine Acyltransferase 3 in the Induction of Macrophage Polarization in PMA-Treated U937 Cells (2015)
  • Author(s): Taniguchi K, Hikiji H, Okinaga T, Hashidate-Yoshida T, Shindou H, Ariyoshi W, Shimizu T, Tominaga K, Nishihara T
  • Journal Title: J Cell Biochem Volume: 116 Issue: 12 Pages: 2840-2848
  • DOI: 10.1002/jcb.25230
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Selective inhibitors of a PAF biosynthetic enzyme lysophosphatidylcholine acyltransferase 2. (2014)
  • Author(s): Tarui M, Shindou H, Kumagai K, Morimoto R, Harayama T, Hashidate T, Kojima H, Okabe T, Nagano T, Nagase T, Shimizu T.
  • Journal Title: J Lipid Res Volume: 55 Pages: 1386-1396
  • Peer Reviewed
• [Journal Article] Diversity and function of membrane glycerophospholipids generated by the remodeling pathway in mammalian cells. (2014)
  • Author(s): Hishikawa, D., Hashidate, T., Shimizu, T., and Shindou, H.
  • Journal Title: J. Lipid Res. Volume: 55 Issue: 5 Pages: 799-807
  • DOI: 10.1194/jlr.r046094
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] The role of lysophosphatidylcholine acyltransferase 3 (LPCAT3) modulating triacylglycerol transport (2015)
  • Author(s): Tomomi Hashidate-Yoshida, Takeshi Harayama, Daisuke Hishikawa, Ryo Morimoto, Fumie Hamano, Suzumi M. Tokuoka, Miki Eto, Yoshihiro Kita, Hideo Shindou, and Takao Shimizu
  • Organizer: BMB2015
  • Place of Presentation: 神戸（神戸ポートアイランド）
  • Year and Date: 2015-12-03
• [Presentation] リゾホスファチジルコリンアシル転移酵素３（LPCAT3）によるトリアシルグリセロール輸送の調節機構 (2015)
  • Author(s): 橋立（吉田）智美、原山武士、菱川大介、森本亮、浜野文三江、徳岡涼美、衛藤樹、北芳博、進藤英雄、清水孝雄
  • Organizer: 第57回日本脂質生化学会
  • Place of Presentation: 東京（一橋大学一橋講堂）
  • Year and Date: 2015-05-29