| Project/Area Number |
16K08607
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Akita University |
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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)
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| 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)
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| Project Period (FY) |
2016-10-21 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥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)
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| 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 |
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| 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.
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| 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。
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