- 作者：Luis F. Menezes ; Cheng-Chao Lin ; Fang Zhou ; Gregory G. Germino
- 关键词：Polycystic kidney disease ; Autosomal Dominant Polycystic Kidney Disease ; Pkd1 ; ADPKD ; Mouse model ; Systems biology ; Metabolism ; Fatty acid oxidation ; Fatty acid oxidation defect ; Lipid metabolism ; Diet
- 刊名：EBioMedicine
- 出版年：2016
- 出版时间：March 2016
- 年：2016
- 卷：5
- 期：Complete
- 页码：183-192
- 全文大小：1438 K
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Adult female mice have slower kidney disease progression than males in an orthologous Pkd1 model of ADPKD.
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Omics and in vitro studies suggest Pkd1 deletion causes cell autonomous metabolic changes and fatty acid oxidation impairment.
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Transcriptional sexual dimorphism in mouse kidneys is consistent with lipid metabolism modifying PKD progression in females.
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Lower lipid content in diet correlates with slower PKD progression.
Autosomal Dominant Polycystic Kidney Disease (ADPKD) is caused by mutations in PKD1 or PKD2 and characterized by the replacement of kidney parenchyma by cysts. Recent studies have identified metabolic differences and increased glycolysis in ADPKD. We now examine the effects of acquired loss of Pkd1 in adult mouse kidney as it transitions from normal to cystic state. We report females have less severe kidney disease and suggest metabolic differences could underlie this protection. Notably, we did not find altered glycolysis, but rather that Pkd1- cells have impaired fatty acid oxidation. We also showed that reducing the fat content in mouse diet correlated with less severe cystic kidney disease. Our results thus support the notion that abnormalities in lipid metabolism are an intrinsic component of ADPKD.