Deletion of cardiac fibroblast growth factor-23 beneficially impacts myocardial energy metabolism in left ventricular hypertrophy

Title (eng)
Deletion of cardiac fibroblast growth factor-23 beneficially impacts myocardial energy metabolism in left ventricular hypertrophy
Author
Nejla Latic
Author
Arezou Lari
Author
Na Sun
Author
Ana Zupcic
Author
Mhaned Oubounyt
Author
Juliana Falivene
Author
Achim Buck
Author
Martin Hofer
Author
Wenhan Chang
Author
Wolfgang M. Kuebler
Author
Jan Baumbach
Author
Axel K. Walch
Author
Alexander Grabner
Author
Reinhold G. Erben
Abstract (eng)
Left ventricular hypertrophy (LVH) is associated with increased cardiac expression of fibroblast growth factor-23 (FGF23) in mice and men. To further elucidate the role of cardiac FGF23 in LVH, we specifically ablated Fgf23 in cardiomyocytes, and employed transverse aortic constriction (TAC) to induce LVH by pressure overload. LVH developed independently of cardiac FGF23, but cardiomyocyte-specific Fgf23 knock-out (Fgf23CKO) TAC mice were characterized by ameliorated hypertension and a distinct reduction of cardiac fibrosis, relative to Fgf23fl/fl TAC controls. Spatial metabolomics revealed reduced intracellular glucose abundance and lowered cardiac energy charge in Fgf23CKO TAC mice, whereas treatment of cultured cardiomyocytes with FGF23 increased intracellular glucose abundance. Spatial transcriptomics showed a downregulation of glucose transporters and glycolytic enzymes, but an upregulation of enzymes involved in fatty acid oxidation in Fgf23CKO TAC mice. These findings suggest that reduced cardiac FGF23 signaling promotes cardiac metabolic health by downregulating glucose consumption and favoring fatty acid oxidation.
Keywords (eng)
Endocrine System And Metabolic DiseasesMetabolismMetabolomics
Type (eng)
journal article
Language
[eng]
Persistent identifier
https://phaidra.vetmeduni.ac.at/o:5100
DOI
10.1038/s44324-025-00087-w
Is in series
Title (eng)
npj Metabolic Health and Disease
Volume
3
Issue
1
ISSN
2948-2828
Issued
2025
Number of pages
14
Publication
Springer
Version type (eng)
version of record (published version)
Date issued
2025
Access rights (eng)
open access
License
CC BY 4.0 International
Rights statement (eng)
© 2025, The Author(s)