ArticleCell death discovery2025
High-fat diet promotes lipotoxicity in the podocytes of uninephrectomized mice: a targeted lipidomics and kidney podocyte-specific analysis.
Article in Cell death discovery, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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Who cites it
6 citing papers in PubMed.
- Role of mitochondria-associated ER membranes in lipid metabolism: implications for renal lipotoxicity.Bioscience reports · 2026Review
- Urotensin II Receptor Deletion Mitigates Kidney Injury and Renal Lipid Remodeling in Mice Fed a Long-Term High-Fat Diet.FASEB bioAdvances · 2026Article
- Review
- Lipid metabolism drives podocyte injury in diabetic kidney disease.Frontiers in immunology · 2026Review
- MASLD: Lipotoxicity and Imaging Parallels from Liver Steatosis to Kidney Injury.Life (Basel, Switzerland) · 2025Review
- The Lipid-Oxidative Stress Axis: Novel Therapeutic Targets for Podocytopathy.Journal of inflammation research · 2025Review
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
Abnormal lipid metabolism is an independent risk factor for kidney injury, significantly altering the associated gene expression, particularly in single kidney models. This study investigates the impact of high-fat diet-induced lipid metabolism on podocyte injury in uninephrectomized mice. Using targeted lipidomics analysis and podocyte-specific assays, the modification of lipid profiles attributed to a high-fat diet and the development of podocyte injury caused by lipid metabolism in mice that underwent unilateral nephrectomy were examined. Mice that underwent unilateral nephrectomy and were fed with a high-fat diet for 13 weeks exhibited progressive renal dysfunction, including the accumulation of lipid droplets in podocytes, vacuolization of tubular cells, and glomerular hypertrophy. Liquid chromatography-triple quadrupole mass spectrometry confirmed a significant increase in cholesteryl ester 20:4 levels in the podocytes of these mice. In vitro, cholesteryl ester 20:4 treatment reduced mitochondrial respiration capacity and mitochondrial glycolysis in podocytes. Furthermore, the treatment led to alterations in the protein expression levels associated with lipid metabolism and transport, mitochondrial activity, and autophagy, including ATP binding cassette subfamily A member 1 (ABCA1), carnitine palmitoyltransferase 1 A (CPT1A), acyl-CoA cholesterol acyltransferase (ACAT), nuclear respiratory factor ½ (NRF½), dynamin-1-like protein (DRP1), and p62. Transcriptome sequencing analysis revealed impaired gene expression, which was associated with the progression of renal fibrosis in unilateral nephrectomy mice with a high-fat diet. Specifically, the expression of matrix metalloproteinases and collagen genes, including fibronectin and collagen IV, was upregulated, indicating fibrosis progression. In conclusion, lipidomics analysis identifies cholesteryl ester 20:4 as a key lipid metabolite accumulating in podocytes, which is associated with mitochondrial dysfunction and abnormal autophagy. This accumulation potentially contributes to structural and functional deterioration in the kidney and highlights its role in kidney damage and its potential as a therapeutic target in metabolic kidney diseases.
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Registered trials
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