ArticleThe Journal of biological chemistry2019
Uric acid activates aldose reductase and the polyol pathway for endogenous fructose and fat production causing development of fatty liver in rats.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers, 1 of them a synthesis that pooled it.
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Who cites it
70 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- Serum Uric Acid and Cardiovascular or All-Cause Mortality in Peritoneal Dialysis Patients: A Systematic Review and Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- The impact of dietary sodium and fructose on renal sodium handling and blood pressure in healthy adults.Physiological reports · 2025Trial
- Fructose directly remodels the translocase of the outer membrane to impair oxidative phosphorylation in podocytes.Signal transduction and targeted therapy · 2026Article
- Fructose: metabolic signal and modern hazard.Nature metabolism · 2026Review
- Serum uric acid and its metabolism-a vital factor in the inflammatory transformation of cancer.Journal of advanced research · 2026Review
- Association between uric acid and non-alcoholic fatty liver disease in patients with hypertension.PloS one · 2026Article
- High-altitude hyperuricemia: a double-edged sword of adaptation and maladaptation.Frontiers in public health · 2026Article
- New Insight Into Male Infertility: Deviation From Basic Tenets of Life.Oxidative medicine and cellular longevity · 2026Review
- Metabolic and Vascular Inflammation in Alopecia Areata: Linking Uric Acid, Lipid Imbalance and ICAM-1 Upregulation.Experimental dermatology · 2025Article
- Sexual dimorphism in zebrafish liver proteins and implications for hepatic regeneration and diseases.Scientific reports · 2025Article
- Uric Acid and Preeclampsia: Pathophysiological Interactions and the Emerging Role of Inflammasome Activation.Antioxidants (Basel, Switzerland) · 2025Review
- From Liver to Kidney: The Overlooked Burden of Nonalcoholic Fatty Liver Disease in Chronic Kidney Disease.Journal of clinical medicine · 2025Review
- Aldose reductase, fructose and fat production in the liver.The Biochemical journal · 2025Review
- NFAT5: a stress-related transcription factor with multiple functions in health and disease.Cell stress · 2025Review
- Association Between Uric Acid to HDL-C Ratio and Metabolic Dysfunction-Associated Steatotic Liver Disease in Type 2 Diabetes Mellitus: A Cross-Sectional Study.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Strong genetic effect on gout revealed by genetic risk score from meta-analysis of two genome-wide association studies.Human cell · 2024Article
- Heterogeneous response of estimated insulin sensitivity indices to metformin in young individuals with type 1 diabetes and different phenotypes.Diabetology & metabolic syndrome · 2024Article
- Regulation of Fructose Metabolism in Nonalcoholic Fatty Liver Disease.Biomolecules · 2024Review
- A genome-first approach to variants in MLXIPL and their association with hepatic steatosis and plasma lipids.Hepatology communications · 2024Article
- Circulating Bone morphogenetic protein 9 (BMP9) as a new biomarker for noninvasive stratification of nonalcoholic fatty liver disease and metabolic syndrome.Clinical and experimental medicine · 2024Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Dietary, fructose-containing sugars have been strongly associated with the development of nonalcoholic fatty liver disease (NAFLD). Recent studies suggest that fructose also can be produced via the polyol pathway in the liver, where it may induce hepatic fat accumulation. Moreover, fructose metabolism yields uric acid, which is highly associated with NAFLD. Here, using biochemical assays, reporter gene expression, and confocal fluorescence microscopy, we investigated whether uric acid regulates aldose reductase, a key enzyme in the polyol pathway. We evaluated whether soluble uric acid regulates aldose reductase expression both in cultured hepatocytes (HepG2 cells) and in the liver of hyperuricemic rats and whether this stimulation is associated with endogenous fructose production and fat accumulation. Uric acid dose-dependently stimulated aldose reductase expression in the HepG2 cells, and this stimulation was associated with endogenous fructose production and triglyceride accumulation. This stimulatory mechanism was mediated by uric acid-induced oxidative stress and stimulation of the transcription factor nuclear factor of activated T cells 5 (NFAT5). Uric acid also amplified the effects of elevated glucose levels to stimulate hepatocyte triglyceride accumulation. Hyperuricemic rats exhibited elevated hepatic aldose reductase expression, endogenous fructose accumulation, and fat buildup that was significantly reduced by co-administration of the xanthine oxidase inhibitor allopurinol. These results suggest that uric acid generated during fructose metabolism may act as a positive feedback mechanism that stimulates endogenous fructose production by stimulating aldose reductase in the polyol pathway. Our findings suggest an amplifying mechanism whereby soft drinks rich in glucose and fructose can induce NAFLD.
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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.