https://phaidra.vetmeduni.ac.at/o:5100 Deletion of cardiac fibroblast growth factor-23 beneficially impacts myocardial energy metabolism in left ventricular hypertrophy Latic, Nejla Nejla Latic 0000-0001-5635-5175 University of Veterinary Medicine Vienna Lari, Arezou Arezou Lari Sun, Na Na Sun Zupcic, Ana Ana Zupcic 0000-0002-9456-7192 University of Veterinary Medicine Vienna Oubounyt, Mhaned Mhaned Oubounyt Falivene, Juliana Juliana Falivene Buck, Achim Achim Buck Hofer, Martin Martin Hofer University of Veterinary Medicine Vienna Chang, Wenhan Wenhan Chang Kuebler, Wolfgang M. Wolfgang M. Kuebler Baumbach, Jan Jan Baumbach Walch, Axel K. Axel K. Walch Grabner, Alexander Alexander Grabner Erben, Reinhold G. Reinhold G. Erben 0000-0003-0801-6958 University of Veterinary Medicine Vienna Springer journal article open access 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. Endocrine System And Metabolic Diseases Metabolism Metabolomics http://creativecommons.org/licenses/by/4.0/ https://phaidra.vetmeduni.ac.at/api/object/o:5100/download 10.1038/s44324-025-00087-w https://phaidra.vetmeduni.ac.at/o:605 application/pdf npj Metabolic Health and Disease issn:2948-2828 VoR npj Metabolic Health and Disease 3 1 3.67 MB 2025