Unraveling the Role of Autophagy in Counteracting Lipotoxicity in the Kidney
Project/Area Number |
15K09260
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Kidney internal medicine
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Research Institution | Osaka University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
猪阪 善隆 大阪大学, 医学系研究科, 教授 (00379166)
高橋 篤史 大阪大学, 医学部附属病院, 助教 (10704786)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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Keywords | オートファジー / 脂肪毒性 / リソソーム / オートファジーフラックス / リポファジー / イコサペント酸エチル / 近位尿細管 / 高脂肪食負荷 / 飢餓 / 尿細管 / ミトコンドリア |
Outline of Final Research Achievements |
Excessive fat intake leads to cellular injury and inflammation (lipotoxicity). Autophagy is a self-degradation process that combats starvation and cellular stress. Here, we studied the effect of lipid overload on lysosomal function and autophagic activity in the kidney. Lipid overload basically stimulates autophagy for renovation of the plasma and organelle membranes, which plays an essential role in maintaining the integrity of proximal tubules. However, this autophagic activation is inevitably accompanied with lysosomal stress and consequent downstream suppression of autophagy, which manifest as phospholipid accumulation in the lysosome. Pharmacological correction by eicosapentaenoic acid restored autophagic flux. We also investigated the autophagy-mediated regulation of renal lipid metabolism during prolonged starvation and elucidated that autophagic degradation of lipid droplets (lipophagy) combats prolonged starvation in the kidney to avoid cellular energy depletion.
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Report
(4 results)
Research Products
(17 results)
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[Journal Article] High-Fat Diet-Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney.2017
Author(s)
Yamamoto T, Takabatake Y, Takahashi A, Kimura T, Namba T, Matsuda J, Minami S, Kaimori JY, Matsui I, Matsusaka T, Niimura F, Yanagita M, Isaka Y.
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Journal Title
Journal of the American Society of Nephrology
Volume: 印刷中
Issue: 5
Pages: 1534-1551
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] High Fat Diet-Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to the Lipotoxicity in the Kidney2016
Author(s)
Yamamoto T, Takabatake Y, Takahashi A, Kimura T, Namba T, Matsuda J, Minami S, Matsusaka T, Niimura F, Yanagita M, Isaka Y.
Organizer
American Society of Nephrology Kidney Week 2016
Place of Presentation
シカゴ, アメリカ
Year and Date
2016-11-19
Related Report
Int'l Joint Research
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