ArticleArthritis research & therapy2022
Xanthine oxidase inhibitor urate-lowering therapy titration to target decreases serum free fatty acids in gout and suppresses lipolysis by adipocytes.
Article in Arthritis research & therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 21 citations in OpenAlex.
- Metformin repurposing in gout: enhancing febuxostat efficacy through anti-inflammatory and metabolic modulation: a randomized controlled double-blind study.Inflammopharmacology · 2026Trial
- Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement and inflammation modulators.Scientific reports · 2024Trial
- Effects of Febuxostat Therapy on Circulating Adipokine Profiles in Patients with Overweight or Obesity and Asymptomatic Hyperuricemia: A Randomized Controlled Study.Obesity facts · 2024Trial
- Uric Acid Extremes and Lipid Dysregulation: Evidence from a Large Population-Based Study.Metabolites · 2026Article
- Treat-to-Target Urate-lowering Therapy: Lessons Learned from the STOP Gout Study.Current rheumatology reports · 2026Review
- Colchicine Suppresses Adipogenic Differentiation of Mesenchymal Stem Cells: Implications for Bone Adiposity Control.Pharmaceutics · 2026Article
- Efficacy of very low calorie diet in the intervention of obesity and the changes in oral microbiota: a prospective cohort study.Journal of translational medicine · 2026Observational
- Fatty acid metabolism in gouty arthritis: mechanisms to therapeutic targeting.Frontiers in immunology · 2025Review
- Association of Metabolic Score for Visceral Fat (METS-VF) with Gout Risk in Patients with Hypertension and Hyperuricemia: A Multicenter Study Based on the Chinese Population.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Effective xanthine oxidase inhibitor urate lowering therapy in gout is linked to an emergent serum protein interactome of complement activation and inflammation modulators.Research square · 2024Article
- Sustained xanthine oxidase inhibitor treat to target urate lowering therapy rewires a tight inflammation serum protein interactome.Research square · 2024Article
- Predictors of Inadequate Serum Urate Response to Low-Dose Febuxostat in Male Patients with Gout.Journal of inflammation research · 2024Article
- Causal impact of human blood metabolites and metabolic pathways on serum uric acid and gout: a mendelian randomization study.Frontiers in endocrinology · 2024Article
- Regulating Lipid Metabolism in Gout: A New Perspective with Therapeutic Potential.International journal of general medicine · 2024Review
- Gas Chromatography-Mass Spectrometry Reveals Stage-Specific Metabolic Signatures of Ankylosing Spondylitis.Metabolites · 2023Article
- Epigenetic and Metabolic Regulation of Macrophages during Gout.Gout, urate, and crystal deposition disease · 2023Article
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
objectiveLinked metabolic and cardiovascular comorbidities are prevalent in hyperuricemia and gout. For mechanistic insight into impact on inflammatory processes and cardiometabolic risk factors of xanthine oxidase inhibitor urate-lowering therapy (ULT) titration to target, we performed a prospective study of gout serum metabolomes from a ULT trial.
methodsSera of gout patients meeting the 2015 ACR/EULAR gout classification criteria (n = 20) and with hyperuricemia were studied at time zero and weeks 12 and 24 of febuxostat or allopurinol dose titration ULT. Ultrahigh performance liquid chromatography-tandem mass spectroscopy acquired the serum spectra. Data were assessed using the Metabolon and Metaboloanalyst software. Lipolysis validation assays were done in febuxostat and/or colchicine-treated 3T3-L1 differentiated adipocytes.
resultsSerum urate decreased from time zero (8.21 ±1.139 SD) at weeks 12 (5.965 ± 1.734 SD) and 24 (5.655 ±1.763 SD). Top metabolites generated by changes in nucleotide and certain amino acid metabolism and polyamine pathways were enriched at 12 and 24 weeks ULT, respectively. Decreases in multiple fatty acid metabolites were observed at 24 weeks, linked with obesity. In cultured adipocytes, febuxostat significantly decreased while colchicine increased the lipolytic response to β-adrenergic-agonism or TNF.
conclusionMetabolomic profiles linked xanthine oxidase inhibitor-based ULT titration to target with reduced serum free fatty acids. In vitro validation studies revealed that febuxostat, but not colchicine, reduced lipolysis in cultured adipocytes. Since soluble urate, xanthine oxidase inhibitor treatment, and free fatty acids modulate inflammation, our findings suggest that by suppressing lipolysis, ULT could regulate inflammation in gout and comorbid metabolic and cardiovascular disease.
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