2017 Fiscal Year Final Research Report
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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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 |
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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Free Research Field |
腎臓内科
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