ArticleJCI insight2024
Uric acid formation is driven by crosstalk between skeletal muscle and other cell types.
Article in JCI insight, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 25 citations in OpenAlex.
- Pharmacokinetics, Safety and Tolerability of HPP737, a Novel PDE4 Inhibitor, in Healthy Chinese Participants: Phase I Study.Drug design, development and therapy · 2026Trial
- Adenylosuccinate acts as a novel pro-angiogenic factor.Research square · 2026Article
- Antioxidant malic-acid-derived lipid nanoparticles delivering secretory uricase circRNA for hyperuricemia and complication management in mice.Nature communications · 2026Article
- Purine metabolism enhances neovascularization of type H vessels in the induced membrane technique.JCI insight · 2026Article
- Association between skeletal muscle index and kidney stones in health screening populations: a single-center cross-sectional study.Translational andrology and urology · 2026Article
- Association between serum uric acid and muscle function in underweight young women: An exploratory cross-sectional study.PloS one · 2026Article
- Computerized tomography-derived body composition metrics are associated with 24-h urine lithogenic parameters.BJUI compass · 2026Article
- Decoding the Uric Acid to HDL Cholesterol Ratio (UHR) as a Novel Metabolic Biomarker for Chronic Pain: Insights Into Precision Diagnostics and Management.Pain research & management · 2026Article
- Association of serological biomarkers with muscle strength and function in sarcopenia: a cross-sectional study.Annals of medicine · 2025Article
- Construction and validation of a nomogram for screening for sarcopenia in patients with osteoporotic vertebral compression fracture.Scientific reports · 2025Article
- Observational
- Research on related factors of hyperuricemia in high altitude area migrant population.Frontiers in endocrinology · 2025Article
- Article
- The impact of uric acid on musculoskeletal diseases: clinical associations and underlying mechanisms.Frontiers in endocrinology · 2025Review
- Muscle quality index and hyperuricemia: adipose tissue as a mediator.Frontiers in endocrinology · 2025Article
- Relationship between uric acid to high-density lipoprotein cholesterol ratio and sarcopenia in NHANES: exploring the mediating role of bilirubin and association with all-cause mortality.Frontiers in nutrition · 2025Article
- A tryptophan-derived uremic metabolite/Ahr/Pdk4 axis governs skeletal muscle mitochondrial energetics in chronic kidney disease.JCI insight · 2024Article
- Immunological Profile and Markers of Endothelial Dysfunction in Elderly Patients with Cognitive Impairments.International journal of molecular sciences · 2024Article
- Comparative metabolomic analysis of spaghetti meat and wooden breast in broiler chickens: unveiling similarities and dissimilarities.Frontiers in physiology · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperuricemia is implicated in numerous pathologies, but the mechanisms underlying uric acid production are poorly understood. Using a combination of mouse studies, cell culture studies, and human serum samples, we sought to determine the cellular source of uric acid. In mice, fasting and glucocorticoid treatment increased serum uric acid and uric acid release from ex vivo-incubated skeletal muscle. In vitro, glucocorticoids and the transcription factor FoxO3 increased purine nucleotide degradation and purine release from differentiated muscle cells, which coincided with the transcriptional upregulation of AMP deaminase 3, a rate-limiting enzyme in adenine nucleotide degradation. Heavy isotope tracing during coculture experiments revealed that oxidation of muscle purines to uric acid required their transfer from muscle cells to a cell type that expresses xanthine oxidoreductase, such as endothelial cells. Last, in healthy women, matched for age and body composition, serum uric acid was greater in individuals scoring below average on standard physical function assessments. Together, these studies reveal skeletal muscle purine degradation is an underlying driver of uric acid production, with the final step of uric acid production occurring primarily in a nonmuscle cell type. This suggests that skeletal muscle fiber purine degradation may represent a therapeutic target to reduce serum uric acid and treat numerous pathologies.
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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.