| Project/Area Number |
18K14964
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Osaka Ohtani University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 糖尿病 / 遺伝子治療 / 脂肪毒性 / アデノウイルスベクター / 脂質 / 生活習慣病 / GWAS |
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| Outline of Final Research Achievements |
I investigated the association between lipoprotein lipase (LPL) overexpression in the liver of a mouse and the suppression of lipotoxicity, which has effects on type 2 diabetes mellitus (T2DM). Mice were transduced with an LPL-expressing Ad vector (Ad-LPL) and simultaneously fed with high-fat diet (HFD). The lipid-droplet formation in the liver decreased in the Ad-LPL-treated mice relative to that in the control mice. Glucose tolerance was significantly higher in the Ad-LPL-treated mice than in the control mice. Furthermore, fasting blood glucose, insulin concentrations, and the extent of hepatic inflammation were significantly lower in the Ad-LPL-treated mice than in the control mice. These results suggest that LPL overexpression in HFD-fed mice attenuates the accumulation of lipid droplets in the liver and improves glucose metabolism. This approach may be helpful in the development of new drugs for treating metabolic syndrome, including T2DM and non-alcoholic fatty liver disease.
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| Academic Significance and Societal Importance of the Research Achievements |
従来の2型糖尿病治療に対する遺伝子治療の試みとしては、インスリン分泌促進のために膵臓を標的としたもの等が主に報告されてきた。一方で、脂質代謝に関連する遺伝子を用いて2型糖尿病の遺伝子治療を行った本研究は、新しい試みであった。そして、本研究により、脂質代謝に関与する遺伝子LPLを用いてマウスに2型糖尿病に対する遺伝子治療を行ったところ、糖代謝異常が改善し、2型糖尿病に対して治療効果が示された。以上より、本研究は、2型糖尿病の新たな治療、医薬品開発、予防につながることが期待される。
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