Tubular CPT1A deletion minimally affects aging and chronic kidney injury
Kidney tubules use fatty acid oxidation (FAO) to support their high energetic requirements. Carnitine palmitoyltransferase 1A (CPT1A) is the rate-limiting enzyme for FAO, and it is necessary to transport long-chain fatty acids into mitochondria. To define the role of tubular CPT1A in aging and injury, we generated mice with tubule-specific deletion of Cpt1a (Cpt1aCKO mice), and the mice were either aged for 2 years or injured by aristolochic acid or unilateral ureteral obstruction. Surprisingly, Cpt1aCKO mice had no significant differences in kidney function or fibrosis compared with wild-type mice after aging or chronic injury. Primary tubule cells from aged Cpt1aCKO mice had a modest decrease in palmitate oxidation but retained the ability to metabolize long-chain fatty acids. Very-long-chain fatty acids, exclusively oxidized by peroxisomes, were reduced in kidneys lacking tubular CPT1A, consistent with increased peroxisomal activity. Single-nuclear RNA-Seq showed significantly increased expression of peroxisomal FAO enzymes in proximal tubules of mice lacking tubular CPT1A. These data suggest that peroxisomal FAO may compensate in the absence of CPT1A, and future genetic studies are needed to confirm the role of peroxisomal β-oxidation when mitochondrial FAO is impaired.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:9 |
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| Enthalten in: |
JCI insight - 9(2024), 6 vom: 22. Feb. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hammoud, Safaa [VerfasserIn] |
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| Links: |
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| Themen: |
CPT1B protein, mouse |
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| Anmerkungen: |
Date Completed 25.03.2024 Date Revised 29.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1172/jci.insight.171961 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370064607 |
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| 520 | |a Kidney tubules use fatty acid oxidation (FAO) to support their high energetic requirements. Carnitine palmitoyltransferase 1A (CPT1A) is the rate-limiting enzyme for FAO, and it is necessary to transport long-chain fatty acids into mitochondria. To define the role of tubular CPT1A in aging and injury, we generated mice with tubule-specific deletion of Cpt1a (Cpt1aCKO mice), and the mice were either aged for 2 years or injured by aristolochic acid or unilateral ureteral obstruction. Surprisingly, Cpt1aCKO mice had no significant differences in kidney function or fibrosis compared with wild-type mice after aging or chronic injury. Primary tubule cells from aged Cpt1aCKO mice had a modest decrease in palmitate oxidation but retained the ability to metabolize long-chain fatty acids. Very-long-chain fatty acids, exclusively oxidized by peroxisomes, were reduced in kidneys lacking tubular CPT1A, consistent with increased peroxisomal activity. Single-nuclear RNA-Seq showed significantly increased expression of peroxisomal FAO enzymes in proximal tubules of mice lacking tubular CPT1A. These data suggest that peroxisomal FAO may compensate in the absence of CPT1A, and future genetic studies are needed to confirm the role of peroxisomal β-oxidation when mitochondrial FAO is impaired | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic kidney disease | |
| 650 | 4 | |a Fatty acid oxidation | |
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| 700 | 1 | |a Osaki, Yosuke |e verfasserin |4 aut | |
| 700 | 1 | |a Funk, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Haichun |e verfasserin |4 aut | |
| 700 | 1 | |a Viquez, Olga |e verfasserin |4 aut | |
| 700 | 1 | |a Delgado, Rachel |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Dongliang |e verfasserin |4 aut | |
| 700 | 1 | |a Phillips Mignemi, Melanie |e verfasserin |4 aut | |
| 700 | 1 | |a Tonello, Jane |e verfasserin |4 aut | |
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