| Project/Area Number |
15K09022
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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 |
Gastroenterology
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
岩渕 和久 順天堂大学, 公私立大学の部局等, 助教授 (10184897)
池嶋 健一 順天堂大学, 医学部, 教授 (20317382)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | リピドラフト / インスリン抵抗性 / NASH / 遊離脂肪酸 |
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| Outline of Final Research Achievements |
In isolated hepatocytes, incubation with palmitic acid (PA) resulted in accumulation of lipid droplets in cytosol. Under confocal microscopy, cells expressing clustered lipid rafts were significantly increased by PA. Addition of cholesterol oxidase (CHOX), which disrupts lipid rafts, to the cultures for 1hr reversed PA-induced clusters. pIRS-1 and -2 and pAkt in response to insulin stimulation were significantly attenuated under PA compared to controls. By contrast, CHOX significantly ameliorated PA induced-insulin resistance. PA alone did not increase ROS, however, low dose of tert-butylhydroperoxide (TBH) obviously caused cell death in PA-pretreated cells. Interestingly, pre-treatment with CHOX significantly prevented increases in ROS and cell death caused by PA plus TBH. PA elicits hepatic insulin resistance and sensitization to oxidative cell injury through clusterization of lipid rafts in isolated hepatocytes.
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