{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004238138372864.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1681/asn.2016070731"}},{"identifier":{"@type":"URI","@value":"https://journals.lww.com/00001751-201705000-00024"}},{"identifier":{"@type":"PMID","@value":"27932476"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"High-Fat Diet–Induced Lysosomal Dysfunction and Impaired Autophagic Flux Contribute to Lipotoxicity in the Kidney"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Excessive fat intake contributes to the progression of metabolic diseases <jats:italic toggle=\"yes\">via</jats:italic> cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic acid, autophagic degradation activity progressively stagnated in association with impaired lysosomal acidification and excessive lipid accumulation. Pulse-chase experiments revealed that the accumulated lipids originated from cellular membranes. In mice with induced PTC-specific ablation of autophagy, PTCs of HFD-mice exhibited greater accumulation of ubiquitin-positive protein aggregates normally removed by autophagy than did PTCs of mice fed a normal diet. Furthermore, HFD-mice had no capacity to augment autophagic activity upon another pathologic stress. Autophagy ablation also exaggerated HFD-induced mitochondrial dysfunction and inflammasome activation. Moreover, renal ischemia-reperfusion induced greater injury in HFD-mice than in mice fed a normal diet, and ablation of autophagy further exacerbated this effect. Finally, we detected similarly enhanced phospholipid accumulation in enlarged lysosomes and impaired autophagic flux in the kidneys of obese patients compared with nonobese patients. These findings provide key insights regarding the pathophysiology of lipotoxicity in the kidney and clues to a novel treatment for obesity-related kidney diseases.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004238138372610","@type":"Researcher","foaf:name":[{"@value":"Takeshi Yamamoto"}],"jpcoar:affiliationName":[{"@value":"Departments of *Nephrology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1030003658597496322","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"30403075"},{"@type":"NRID","@value":"1000030403075"},{"@type":"NRID","@value":"9000014207598"},{"@type":"NRID","@value":"9000396131757"},{"@type":"NRID","@value":"9000391778001"},{"@type":"NRID","@value":"9000398823877"},{"@type":"NRID","@value":"9000397656920"},{"@type":"NRID","@value":"9000411249236"},{"@type":"NRID","@value":"9000368417786"},{"@type":"NRID","@value":"9000399224818"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/takaba-handai3857"}],"foaf:name":[{"@value":"Yoshitsugu Takabatake"}],"jpcoar:affiliationName":[{"@value":"Departments of *Nephrology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1420001326217557248","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10704786"},{"@type":"NRID","@value":"1000010704786"},{"@type":"NRID","@value":"9000002136160"},{"@type":"NRID","@value":"9000007843100"},{"@type":"NRID","@value":"9000405896311"},{"@type":"NRID","@value":"9000396131755"},{"@type":"NRID","@value":"9000360546031"},{"@type":"NRID","@value":"9000264266074"},{"@type":"NRID","@value":"9000021665175"},{"@type":"NRID","@value":"9000356640472"},{"@type":"NRID","@value":"9000241863318"},{"@type":"NRID","@value":"9000398586216"},{"@type":"NRID","@value":"9000398585535"},{"@type":"NRID","@value":"9000009812046"},{"@type":"NRID","@value":"9000253393802"},{"@type":"NRID","@value":"9000411249230"},{"@type":"NRID","@value":"9000399224828"},{"@type":"NRID","@value":"9000412351683"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/takahashi-handai3857"}],"foaf:name":[{"@value":"Atsushi Takahashi"}],"jpcoar:affiliationName":[{"@value":"Departments of *Nephrology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004238138372744","@type":"Researcher","foaf:name":[{"@value":"Tomonori Kimura"}],"jpcoar:affiliationName":[{"@value":"Departments of *Nephrology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1420282801196519168","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"30734420"},{"@type":"NRID","@value":"1000030734420"},{"@type":"NRID","@value":"9000001437378"},{"@type":"NRID","@value":"9000242123927"},{"@type":"NRID","@value":"9000020559230"},{"@type":"NRID","@value":"9000396131754"},{"@type":"NRID","@value":"9000018608328"},{"@type":"NRID","@value":"9000254512977"},{"@type":"NRID","@value":"9000254100029"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/namba-handai3857"}],"foaf:name":[{"@value":"Tomoko Namba"}],"jpcoar:affiliationName":[{"@value":"Departments of *Nephrology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004238138372613","@type":"Researcher","foaf:name":[{"@value":"Jun Matsuda"}],"jpcoar:affiliationName":[{"@value":"Departments of *Nephrology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1420845751157866880","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"00791592"},{"@type":"NRID","@value":"1000000791592"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/minami415"}],"foaf:name":[{"@value":"Satoshi Minami"}],"jpcoar:affiliationName":[{"@value":"Departments of *Nephrology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004238138372737","@type":"Researcher","foaf:name":[{"@value":"Jun-ya Kaimori"}],"jpcoar:affiliationName":[{"@value":"Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan;"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004238138372736","@type":"Researcher","foaf:name":[{"@value":"Isao Matsui"}],"jpcoar:affiliationName":[{"@value":"Departments of *Nephrology and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004238138372867","@type":"Researcher","foaf:name":[{"@value":"Taiji Matsusaka"}],"jpcoar:affiliationName":[{"@value":"Institute of Medical Sciences and Department of Molecular Life Sciences and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004238138372608","@type":"Researcher","foaf:name":[{"@value":"Fumio Niimura"}],"jpcoar:affiliationName":[{"@value":"Department of Pediatrics, Tokai University School of Medicine, Isehara, Kanagawa, Japan; and"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004238138372865","@type":"Researcher","foaf:name":[{"@value":"Motoko Yanagita"}],"jpcoar:affiliationName":[{"@value":"Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004238138372868","@type":"Researcher","foaf:name":[{"@value":"Yoshitaka Isaka"}],"jpcoar:affiliationName":[{"@value":"Departments of *Nephrology and"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"10466673"},{"@type":"EISSN","@value":"15333450"}],"prism:publicationName":[{"@value":"Journal of the American Society of Nephrology"}],"dc:publisher":[{"@value":"Ovid Technologies (Wolters Kluwer Health)"}],"prism:publicationDate":"2016-12-08","prism:volume":"28","prism:number":"5","prism:startingPage":"1534","prism:endingPage":"1551"},"reviewed":"false","url":[{"@id":"https://journals.lww.com/00001751-201705000-00024"}],"createdAt":"2016-12-09","modifiedAt":"2023-08-29","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Male","dc:title":"Male"},{"@id":"https://cir.nii.ac.jp/all?q=Palmitic%20Acid","dc:title":"Palmitic Acid"},{"@id":"https://cir.nii.ac.jp/all?q=Diet,%20High-Fat","dc:title":"Diet, High-Fat"},{"@id":"https://cir.nii.ac.jp/all?q=Kidney","dc:title":"Kidney"},{"@id":"https://cir.nii.ac.jp/all?q=Lipid%20Metabolism","dc:title":"Lipid Metabolism"},{"@id":"https://cir.nii.ac.jp/all?q=Mice","dc:title":"Mice"},{"@id":"https://cir.nii.ac.jp/all?q=Autophagy","dc:title":"Autophagy"},{"@id":"https://cir.nii.ac.jp/all?q=Animals","dc:title":"Animals"},{"@id":"https://cir.nii.ac.jp/all?q=Kidney%20Diseases","dc:title":"Kidney Diseases"},{"@id":"https://cir.nii.ac.jp/all?q=Lysosomes","dc:title":"Lysosomes"}],"project":[{"@id":"https://cir.nii.ac.jp/crid/1040282256827428864","@type":"Project","projectIdentifier":[{"@type":"KAKEN","@value":"15K09260"},{"@type":"JGN","@value":"JP15K09260"},{"@type":"URI","@value":"https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15K09260/"}],"notation":[{"@language":"ja","@value":"腎における脂質毒性抑制機構としてのオートファジーの役割とその病態生理的意義の解明"},{"@language":"en","@value":"Unraveling the Role of Autophagy in Counteracting Lipotoxicity in the Kidney"}]}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050566774879454336","@type":"Article","resourceType":"学術雑誌論文(journal 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macrophages in a TFEB-independent manner."}]},{"@id":"https://cir.nii.ac.jp/crid/1360574093440967296","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"High-fat diet intake accelerates aging, increases expression of Hsd11b1, and promotes lipid accumulation in liver of SAMP10 mouse"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574093593091200","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"After the banquet"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574093911315584","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"Fatty Acid Trafficking in Starved Cells: Regulation by Lipid Droplet Lipolysis, Autophagy, and Mitochondrial Fusion Dynamics"}]},{"@id":"https://cir.nii.ac.jp/crid/1360574094986697856","@type":"Article","relationType":["references"],"jpcoar:relatedTitle":[{"@value":"In Vivo Analysis of Autophagy in Response to Nutrient Starvation Using Transgenic Mice Expressing a Fluorescent 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