ArticleLife metabolism2024
Fatty acid oxidation-induced HIF-1α activation facilitates hepatic urate synthesis through upregulating NT5C2 and XDH.
Article in Life metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- A metabolomic signatures in hyperuricemia: a systematic review.Metabolomics : Official journal of the Metabolomic Society · 2026Pooled it
- Integrated transcriptomics and metabolomics reveal suppression of the PPAR α/γ pathway linking purine metabolism disorder to high-protein diet-induced hyperuricemia in goslings.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Article
- Hyperuricemia and Hypoxic Pulmonary Hypertension: Pathogenic Links, Clinical Evidence, and Emerging Therapeutic Insights.Cardiovascular drugs and therapy · 2026Review
- Identifying causal genetic variants for high-altitude adaptation through blood eQTL analysis in plateau populations.Communications biology · 2026Article
- Potent and Sustained Lowering of Serum Uric Acid by YJH-012-D, a GalNAc-Conjugated siRNA Targeting Xanthine Dehydrogenase.Pharmacology research & perspectives · 2026Article
- Association between dietary fat intake and fatty acid profiles and hyperuricemia among Chinese adults: Results from the China Health and Nutrition Survey.Asia Pacific journal of clinical nutrition · 2026Article
- Article
- Therapeutic potential of traditional Chinese medicine for hyperuricemia: mechanistic insights and clinical prospects.Frontiers in pharmacology · 2026Review
- A Bayesian network-based predictive model for gout onset risk: associations with traditional Chinese medicine constitution in hyperuricemic populations.Frontiers in medicine · 2026Article
- Metabolomic and microbiome integration of Han-Tibetan and plain-plateau populations.BMC biology · 2025Article
- Impact ofMolecules (Basel, Switzerland) · 2025Article
- Fatty acid metabolism in gouty arthritis: mechanisms to therapeutic targeting.Frontiers in immunology · 2025Review
- Association between mixed venous oxygen saturation and serum uric acid levels in patients with heart failure.PloS one · 2025Article
- U-Shaped association between apolipoprotein A1 and serum uric acid levels in patients with osteoporotic fractures: a cross-sectional study.Frontiers in endocrinology · 2025Article
- Tailorable bimetallic nanozyme mitigates intervertebral disc degeneration by inhibiting oxidative stress and inflammageing.Theranostics · 2025Article
- Hyperuricemia in Chinese Patients with Mood Disorders: Prevalence, Related Factors, and Predictive Model.Neuropsychiatric disease and treatment · 2025Article
- Association between Body Mass Index and Serum Uric Acid: mediation analysis involving liver enzymes indicators.BMC public health · 2024Article
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Authors and funding
22 authors.
Funding
Abstract
Dyslipidemia affects approximately half of all people with gout, and prior Mendelian randomization analysis suggested a causal role for elevated triglycerides in hyperuricemia (HU), but the underlying mechanisms remain elusive. We hypothesize that dyslipidemia promotes hepatic urate biosynthesis in HU and gout and fatty acid (FA) oxidation (FAO) drives this process. Here we developed a targeted metabolomics to quantify major metabolites in purine metabolic pathway in the sera of a human cohort with HU, gout, and normaluricemic controls. We found that the levels of major purine metabolites and multiple FAs were significantly elevated in HU and gout groups compared to normouricemic controls, whereas hypoxathine showed opposite trend. Furthermore, the levels of multiple serum FAs were positively correlated with urate, xanthine, and inosine but negatively with hypoxanthine, which was also observed in a murine model of high-fat diet-induced HU. Using a stable isotope-labeled metabolic flux assay, we discovered that exogenous hypoxanthine plays a key role in urate synthesis. Moreover, FAO-induced hypoxia-inducible factor 1 alpha (HIF-1α) activation upregulated 5'-nucleotidase II (NT5C2) and xanthine dehydrogenase (XDH) levels to facilitate hypoxanthine uptake from the blood to the liver and activation of urate biosynthesis. Our findings were further supported by data in human hepatocytes and 50 paired serum and liver tissues from liver transplant donors. Together, this study uncovers a mechanism by which FAO promotes hepatic urate synthesis by activating HIF-1α-NT5C2/XDH pathways, directly linking lipid metabolism to HU.
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