Serum metabolomic profiling uncovered metabolic shifts in individuals upon moderate-altitude exposure and identified the potentiality of beta-alanine to ameliorate hyperuricemia
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BACKGROUND: High-altitude exposure has been associated with an increased risk of hyperuricemia (HU) and gout, though the underlying mechanisms remain poorly understood. METHODS: We conducted a comprehensive analysis of the serum metabolome and phenome in both discovery and validation cohorts of Han Chinese individuals who underwent long-term moderate-altitude exposure (∼12 months), as well as in an independent cohort consisting of local Han Chinese and Tibetans residing in Nyingchi (>5 years). Beta-Alanine intervention was applied in hypoxanthine and potassium oxonate-induced in vitro and in vivo experiments. RESULTS: Individuals exposed to moderate altitude exhibited elevated serum urate and an increase in overall medium-chain fatty acids (MCFAs), coupled with a decrease in overall amino acids (AAs) and short-chain fatty acids (SCFAs). Rmcorr correlation analysis revealed a significant negative association between Beta-Alanine and serum urate, whereas nonanoic acid was in versa, potentially driving lower serum urate in long-term exposed residents. Both in vitro and in vivo experiments demonstrated that Beta-Alanine inhibited xanthine oxidase (XOD) and reversed the HU phenotype in human hepatocytes and mice induced by hypoxanthine (HX) and potassium oxonate (PO), with a urate-lowering effect in mice. Hepatic pathology and transcriptome analysis of HU mice treated with Beta-Alanine indicated that the mechanisms involved the inhibition of XOD, amelioration of the inflammation phenotype in hepatocytes, and promotion of renal urate excretion. Furthermore, the 10-fold cross-validation random forest classification (RFC) predictive modeling based on selected metabolites and phenotypes achieved an area under receiver operating characteristic (ROC) curve (AUC) value of 0.93 (95 % confidence interval (CI): 0.85-1.00) and 0.79 (95 % CI: 0.59-0.98) for distinguishing individuals with high risk of asymptomatic HU (AHU) in the training dataset and validation dataset, respectively. CONCLUSIONS: This study reveals serum urate and metabolome altered in moderate-altitude exposed individuals and Beta-Alanine intervention could ameliorate hyperuricemia. Our findings suggest that targeting the circulating metabolome may pave novel avenues to counter diseases associated with HU.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Serum metabolomic profiling uncovered metabolic shifts in individuals upon moderate-altitude exposure and identified the potentiality of beta-alanine to ameliorate hyperuricemia
- Date Crossref
- 01/04/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Guangdong Academy of Medical Sciences pays non établi dans la noticeÉtablissement de santé
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Guangdong Provincial People's Hospital Department of Neurosurgery pays non établi dans la noticeÉtablissement de santé
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Southern Medical University Guangdong Cardiovascular Institute pays non établi dans la noticeUniversité ou école supérieure
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Ganzhou People's Hospital pays non établi dans la noticeÉtablissement de santé
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Gaozhou People's Hospital pays non établi dans la noticeÉtablissement de santé
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South China University of Technology pays non établi dans la noticeUniversité ou école supérieure
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School of Medicine pays non établi dans la noticeUniversité ou école supérieure
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Nyingchi People's Hospital pays non établi dans la noticeÉtablissement de santé
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Biotree Metabolomics Technology Research Center pays non établi dans la noticeStructure de recherche
Guangdong Academy of Medical Sciences, Department of Neurosurgery — Guangdong Provincial People's Hospital et Guangdong Cardiovascular Institute — Southern Medical University, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.