Elucidation of novel molecular mechanisms and therapeutic targets of hypertriglyceridemia

• Project/Area Number: 15K19506
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: Takanashi Mikio 東京大学, 医学部附属病院, 特任助教 (70610799)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 脂質 / 糖尿病 / インスリン / ホルモン感受性リパーゼ / リポ蛋白リパーゼ / MCTオイル / 脂質異常症 / カイロミクロン

Outline of Final Research Achievements

The molecular mechanism of hypertriglyceridemia is not fully understood, so we do not have adequate therapeutic agents. In insulin deficient status, the plasma level of triglycerides is lower in hormone-sensitive lipase (HSL) deficient mice than in wild-type mice. The current study was aimed at elucidating the novel molecular mechanisms and therapeutic targets of hypertriglyceridemia. HSL-deficient mice and some other lipolytic gene deficient mice were used in this study. Under various statuses (insulin-deficient, treated with triton WR-1339, challenged with olive oil or medium chain triglycerides), we examined the plasma level of triglycerides and gene expressions. Novel molecular mechanism independent of lipoprotein lipase (LPL) was suggested, and which are currently under investigation.

Research Products

• [Presentation] Amelioration of streptozotocin-induced diabetic hypertriglyceridemia in the absence of hormone-sensitive lipase (2016)
  • Author(s): Mikio Takanashi, Satoru Takase, Yoshino Taira, Takeshi Kimura, Sachiko Okazaki, Pengfei Xu, Chengcheng Li, Futoshi Shionoiri, Yoko IIzuka, Jun-ichi Osuga, Shun Ishibashi, Takashi Kadowaki, Hiroaki Okazaki
  • Organizer: American Heart Association Scientific Sessions 2016
  • Place of Presentation: New Orleans, USA
  • Year and Date: 2016-11-12
  • Int'l Joint Research
• [Presentation] インスリン欠乏性高中性脂肪血症の成因におけるホルモン感受性リパーゼの重要な役割 (2015)
  • Author(s): 高梨幹生
  • Organizer: 第47回日本動脈硬化学会総会・学術集会
  • Place of Presentation: 仙台国際センター（宮城県仙台市）
  • Year and Date: 2015-07-09
• [Presentation] インスリン欠乏性高中性脂肪血症に与えるホルモン感受性リパーゼの重要な役割 (2015)
  • Author(s): 高梨幹生
  • Organizer: 第58回日本糖尿病学会年次学術集会
  • Place of Presentation: グランプラス セント・ヴァレンタイン（山口県下関市）
  • Year and Date: 2015-05-21