ArticleDiabetes2019
Proximal Tubular Cell-Specific Ablation of Carnitine Acetyltransferase Causes Tubular Disease and Secondary Glomerulosclerosis.
Article in Diabetes, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
34 citing papers in PubMed, 40 citations in OpenAlex.
- Involvement of impaired carnitine-induced fatty acid oxidation in experimental and human diabetic kidney disease.JCI insight · 2025Trial
- Single-Nucleus Transcriptomic Atlas Reveals Disease-Associated Cellular States in Human Glomerular Diseases.Kidney international reports · 2026Article
- Metabolic determinants of autoimmune kidney diseases.Nature reviews. Nephrology · 2026Review
- Plasma acylcarnitine profiling reveals heart failure-specific fatty acid oxidation signature in chronic kidney disease.Journal of lipid research · 2026Article
- Review
- Kidney-Vascular Metabolic Crosstalk: Altered Lipoproteins in CKD.Circulation research · 2026Review
- Oral octanoylcarnitine alleviates exercise intolerance in mouse models of long-chain fatty acid oxidation disorders.JCI insight · 2025Article
- Targeted Analysis of Serum and Urinary Metabolites for Early Chronic Kidney Disease.International journal of molecular sciences · 2025Article
- Comparative Effects of Monascin and Monascinol Produced byJournal of fungi (Basel, Switzerland) · 2024Article
- Adverse effects of acute tubular injury on the glomerulus: contributing factors and mechanisms.Pediatric nephrology (Berlin, Germany) · 2024Review
- The key role of altered tubule cell lipid metabolism in kidney disease development.Kidney international · 2024Review
- Dysregulated palmitic acid metabolism promotes the formation of renal calcium-oxalate stones through ferroptosis induced by polyunsaturated fatty acids/phosphatidic acid.Cellular and molecular life sciences : CMLS · 2024Article
- Renal Epithelial Mitochondria: Implications for Hypertensive Kidney Disease.Comprehensive Physiology · 2023Article
- Redox regulation in diabetic kidney disease.American journal of physiology. Renal physiology · 2023Review
- GCN5L1-mediated TFAM acetylation at K76 participates in mitochondrial biogenesis in acute kidney injury.Journal of translational medicine · 2022Article
- Signaling pathways of chronic kidney diseases, implications for therapeutics.Signal transduction and targeted therapy · 2022Review
- Intact mitochondrial substrate efflux is essential for prevention of tubular injury in a sex-dependent manner.JCI insight · 2022Article
- Mechanosensitive Piezo1 channels mediate renal fibrosis.JCI insight · 2022Article
- The Effect of SGLT2 Inhibition on Diabetic Kidney Disease in a Model of Diabetic Retinopathy.Biomedicines · 2022Article
- Cholesterol Metabolism in Chronic Kidney Disease: Physiology, Pathologic Mechanisms, and Treatment.Advances in experimental medicine and biology · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Proximal tubular epithelial cells are highly energy demanding. Their energy need is covered mostly from mitochondrial fatty acid oxidation. Whether derailments in fatty acid metabolism and mitochondrial dysfunction are forerunners of tubular damage has been suggested but is not entirely clear. Here we modeled mitochondrial overload by creating mice lacking the enzyme carnitine acetyltransferase (CrAT) in the proximal tubules, thus limiting a primary mechanism to export carbons under conditions of substrate excess. Mice developed tubular disease and, interestingly, secondary glomerulosclerosis. This was accompanied by increased levels of apoptosis regulator and fibrosis markers, increased oxidative stress, and abnormal profiles of acylcarnitines and organic acids suggesting profound impairments in all major forms of nutrient metabolism. When mice with CrAT deletion were fed a high-fat diet, kidney disease was more severe and developed faster. Primary proximal tubular cells isolated from the knockout mice displayed energy deficit and impaired respiration before the onset of pathology, suggesting mitochondrial respiratory abnormalities as a potential underlying mechanism. Our findings support the hypothesis that derailments of mitochondrial energy metabolism may be causative to chronic kidney disease. Our results also suggest that tubular injury may be a primary event followed by secondary glomerulosclerosis, raising the possibility that focusing on normalizing tubular cell mitochondrial function and energy balance could be an important preventative strategy.
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Registered trials
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.