| Project/Area Number |
17K19934
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Health science and related fields
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| Research Institution | Yokohama College of Pharmacy |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
前田 利男 静岡県立大学, 薬学部, 客員教授 (00137069)
斉藤 麻希 岩手医科大学, 薬学部, 助教 (40365185)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | メタボリックシンドローム / 肥満抵抗性 / 高脂肪 / 脂肪肝 / マウス / 肥満 / ｄｄＹ系マウス / 高脂肪食 / ＣＤ３６ / ａｐｏＡ１ / ＮＰＣ１Ｌ１ / インスリン / 耐糖能 / ddY系マウス / apoB / CD36 / レプチン / 肝β2受容体 / グリコーゲン / メカニカルストレス / 脂肪細胞 / マクロファージ / 脂肪組織 |
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| Outline of Final Research Achievements |
Abdominal vibration significantly reduced fat contents of the local adipose tissues and improve glucose intolerance in high-fat-diet (HFD) induced obese mice. We also investigated the obesity-resistant (LEAN) and the obesity-prone (FAT) subpopulations in the outbred colony of mice fed with HFD. LEAN and Fat mice showed significant differences in hepatic glucose- and fat-metabolisms. Hepatic gene expression for fat synthesis and accumulation and steatosis therein were significantly attenuated in LEAN as compared with those in FAT. Also, hepatic glycogen content of LEAN was higher than that of FAT. LEAN showed normal glucose tolerance and insulin sensitivity, whereas FAT showed severe diabetes. In addition, we have isolated the inbred mice showing either LEAN or FAT phenotypes from the original colony. There were sex differences in gene expression of lipid metabolisms in small intestine and liver, and the female LEAN showed more resistant to HFD-induced obesity.
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| Academic Significance and Societal Importance of the Research Achievements |
科学的根拠に乏しかった脂肪組織に対する局所的な物理刺激の効果について、動物実験レベルながら耐糖能など全身の代謝機能にまで及ぶ事を示し、外因性制御の裏付けとなる力学刺激に対する脂肪組織の変化を遺伝子発現レベルで明らかにした。また、内因性の肥満抵抗性機序として、高脂肪食による肥満誘導に抵抗する近交系マウスを確立し、肝・小腸での分子機序の一端を示し、雌において更に強い肥満抵抗性を示すことも見出した。今後、女性の肥満と痩せにおける問題を解明するための有用なツールにもなり得る。
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