过氧化物酶体
肉碱
β氧化
线粒体
内科学
内分泌学
肾
生物
酶
脂毒性
纤维化
新陈代谢
化学
生物化学
受体
医学
胰岛素抵抗
糖尿病
作者
Safaa H. Hammoud,Alla V. Ivanova,Yosuke Osaki,Steven Daniel Funk,Haichun Yang,Olga M. Viquez,Rachel Delgado,Dongliang Lu,Melanie Phillips Mignemi,Jane Tonello,Selene Colon,Louise Lantier,David H. Wasserman,Benjamin D. Humphreys,Jeffrey R. Koenitzer,Justin Kern,Mark P. de Caestecker,Toren Finkel,Agnes B. Fogo,Nidia Messias,Irfan J. Lodhi,Leslie Gewin
出处
期刊:JCI insight
[American Society for Clinical Investigation]
日期:2024-02-22
卷期号:9 (6)
标识
DOI:10.1172/jci.insight.171961
摘要
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.
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