• Jana Alber, Peter Freisinger, and Michael Föller.
• University of Hohenheim, Department of Physiology, Stuttgart, Germany.
• Nutrition. 2022 Apr 1; 96: 111573.

ObjectivesFibroblast growth factor 23 (FGF23) controls the production and degradation of biologically active vitamin D, 1,25(OH)2D3, and phosphate reabsorption in the kidney as a hormone synthesized by bone cells. Additional paracrine effects in other organs exist as well. As a biomarker, the FGF23 plasma concentration increases in renal and cardiovascular diseases, and is correlated with outcome. The regulation of FGF23 is incompletely understood and dependent on several factors, including oxidative stress. L-homocysteine is an amino acid produced in methionine metabolism, and can be converted into further metabolites depending on the availability of vitamin B. Hyperhomocysteinemia is a potential cardiovascular risk factor. Our study aimed to explore whether homocysteine impacts FGF23 synthesis.MethodsExperiments were performed in UMR106 osteoblast-like cells. Fgf23 gene expression and FGF23 protein concentration were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. Oxidative stress was determined by 2',7'-dichlorofluorescein diacetate fluorescence.ResultsHomocysteine dose-dependently upregulated Fgf23 gene expression and protein synthesis. Moreover, homocysteine imposed oxidative stress on UMR106 cells. The effect of homocysteine on Fgf23 was abrogated by antioxidant ascorbic acid.ConclusionsHomocysteine is a potent stimulator of FGF23 production, an effect at least in part mediated by oxidative stress. The homocysteine-dependent upregulation of FGF23 presumably contributes to its role as a cardiovascular risk factor.Copyright © 2021 Elsevier Inc. All rights reserved.

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