Role of lipoprotein lipase on Exercise effects.

• Project/Area Number: 16K08607
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Akita University
• Principal Investigator: Nishijima Kazutoshi 秋田大学, バイオサイエンス教育・研究サポートセンター, 准教授 (70435874)
• Co-Investigator(Kenkyū-buntansha): 西田 裕一郎 佐賀大学, 医学部, 講師 (50530185) ; 新見 学 山梨大学, 大学院総合研究部, 助教 (80644898)
• Project Period (FY): 2016-10-21 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
• Keywords: リポタンパクリパーゼ / 中性脂肪 / ノックアウトウサギ / 脂質代謝異常 / 運動効果 / CRISPR/Cas9 / 脂質代謝 / リポ蛋白リパーゼ / メタボリック症候群 / モデル動物

Outline of Final Research Achievements

We challenged to establish lipoprotein lipase (LPL) knock-out rabbit to investigate the role of lipoprotein lipase which is related with exercise effects. LPL is an essential enzyme for triglyceride (TG) metabolism, and homo-deficient individuals were considered to be lethal. Sequence analysis on
a survived individual with high plasma TG showed some some gene modification around target site of CRISPR/Cas9, which seemed to be heterogenic.
Expression analysis of lipid metabolism-related genes by quantitative PCR was performed on the gene-modified individual and it was shown that PGC-1α, GLUT4, CRT-1, HMG-CoA, FAS were decreased in soleus muscle, and in contrast, expression of PPAR-γ, SREP-2, CPT-1, FAS were increased in the liver.

Academic Significance and Societal Importance of the Research Achievements

LPLは中性脂肪を遊離脂肪酸とグリセロールに加水分解し、血中の中性脂肪を低下させることから肥満・メタボリック症候群の治療ターゲットとなると考えられてきた。しかし、本研究により、LPLの作用は臓器により異なる可能性が示唆され、治療ターゲトとする際には慎重な検討が必要であることが示された。

Research Products

• [Presentation] Effect of inhibin antiserum administration and vulva color on superovulation in rabbit. (2017)
  • Author(s): Nishijima K, Watanabe G, Kitajima S, Basaki K, Fukuda Y, Komatsu Y, Yano M, Obata T, Matsuo Y, Matsuda Y, Seki S.
  • Organizer: 7th International Congress on Rabbit Biotechnology
  • Int'l Joint Research