ArticleThe Journal of clinical investigation2023
ACSS2 gene variants determine kidney disease risk by controlling de novo lipogenesis in kidney tubules.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 36 citations in OpenAlex.
- Perilipin 2 drives cisplatin-induced acute kidney injury in young but not aged kidneys.American journal of physiology. Renal physiology · 2026Article
- Uremic toxins promote renal fatty acid synthesis and fibrosis via activating aryl hydrocarbon receptor.Nature communications · 2026Article
- ACLY-Driven Metabolic Reprogramming Promotes Histone Acetylation and Inflammation-Associated Fibrosis in Chronic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Divergent Liver and Kidney Metabolic Responses to Ketogenic, High-Fat, and Sucrose-Enriched Diets in Mice.Nutrients · 2026Article
- Fatty acid metabolism: opportunities and challenges of traditional Chinese medicine in the treatment of renal fibrosis.Chinese medicine · 2026Review
- Hypertriglyceridemia in chronic kidney disease: pathophysiological mechanisms, cardiovascular risk, and emerging therapeutics.Lipids in health and disease · 2026Review
- Ectopic lipid deposition in kidney diseases: mechanisms in specific cell types and therapeutic strategies.Frontiers in endocrinology · 2026Review
- Kidney-targeted drug delivery: from physiological mechanisms to precision therapeutics.Frontiers in bioengineering and biotechnology · 2026Review
- Kidney angiopoietin-like protein 4 regulates fibrotic responses in diabetic kidney disease.Frontiers in pharmacology · 2026Review
- Renal insulin-like growth factor binding-protein 7 is a critical promoter of progressive diabetic kidney disease.Nature communications · 2025Article
- Role of nuclear receptors, lipid metabolism, and mitochondrial function in the pathogenesis of diabetic kidney disease.American journal of physiology. Renal physiology · 2025Review
- Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- From fat to filter: the effect of adipose tissue-derived signals on kidney function.Nature reviews. Nephrology · 2025Review
- Metabolic reprogramming by endothelial ANGPTL4 depletion protects against diabetic kidney disease.bioRxiv : the preprint server for biology · 2025Article
- How the Renal Tubule May Adapt to Fuel Shortage.Kidney360 · 2025Article
- The actin and microtubule network regulator WHAMM is identified as a key kidney disease risk gene.Cell reports · 2025Article
- ACSS2 and metabolic diseases: from lipid metabolism to therapeutic target.Lipids in health and disease · 2025Review
- A guide to studying 3D genome structure and dynamics in the kidney.Nature reviews. Nephrology · 2025Review
- Mitochondrial dysfunction has a central role in diabetic kidney disease.Nature reviews. Nephrology · 2025Article
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
Abstract
Worldwide, over 800 million people are affected by kidney disease, yet its pathogenesis remains elusive, hindering the development of novel therapeutics. In this study, we used kidney-specific expression of quantitative traits and single-nucleus open chromatin analysis to show that genetic variants linked to kidney dysfunction on chromosome 20 target the acyl-CoA synthetase short-chain family 2 (ACSS2). By generating ACSS2-KO mice, we demonstrated their protection from kidney fibrosis in multiple disease models. Our analysis of primary tubular cells revealed that ACSS2 regulated de novo lipogenesis (DNL), causing NADPH depletion and increasing ROS levels, ultimately leading to NLRP3-dependent pyroptosis. Additionally, we discovered that pharmacological inhibition or genetic ablation of fatty acid synthase safeguarded kidney cells against profibrotic gene expression and prevented kidney disease in mice. Lipid accumulation and the expression of genes related to DNL were elevated in the kidneys of patients with fibrosis. Our findings pinpoint ACSS2 as a critical kidney disease gene and reveal the role of DNL in kidney disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.