phaidra.vetmeduni.ac.at o:5100 DOI 10.1038/s44324-025-00087-w Deletion of cardiac fibroblast growth factor-23 beneficially impacts myocardial energy metabolism in left ventricular hypertrophy 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. eng Endocrine System And Metabolic Diseases Metabolism Metabolomics 2026-05-07T08:06:47.581Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Latic;Nejla; FN:Nejla Latic X-ORCID:https://orcid.org/0000-0001-5635-5175 END:VCARD BEGIN:VCARD VERSION:3.0 N:Lari;Arezou; FN:Arezou Lari END:VCARD BEGIN:VCARD VERSION:3.0 N:Sun;Na; FN:Na Sun END:VCARD BEGIN:VCARD VERSION:3.0 N:Zupcic;Ana; FN:Ana Zupcic X-ORCID:https://orcid.org/0000-0002-9456-7192 END:VCARD BEGIN:VCARD VERSION:3.0 N:Oubounyt;Mhaned; FN:Mhaned Oubounyt END:VCARD BEGIN:VCARD VERSION:3.0 N:Falivene;Juliana; FN:Juliana Falivene END:VCARD BEGIN:VCARD VERSION:3.0 N:Buck;Achim; FN:Achim Buck END:VCARD BEGIN:VCARD VERSION:3.0 N:Hofer;Martin; FN:Martin Hofer END:VCARD BEGIN:VCARD VERSION:3.0 N:Chang;Wenhan; FN:Wenhan Chang END:VCARD BEGIN:VCARD VERSION:3.0 N:Kuebler;Wolfgang M.; FN:Wolfgang M. Kuebler END:VCARD BEGIN:VCARD VERSION:3.0 N:Baumbach;Jan; FN:Jan Baumbach END:VCARD BEGIN:VCARD VERSION:3.0 N:Walch;Axel K.; FN:Axel K. Walch END:VCARD BEGIN:VCARD VERSION:3.0 N:Grabner;Alexander; FN:Alexander Grabner END:VCARD BEGIN:VCARD VERSION:3.0 N:Erben;Reinhold G.; FN:Reinhold G. Erben X-ORCID:https://orcid.org/0000-0003-0801-6958 END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 3847214 https://phaidra.vetmeduni.ac.at/o:5100 https://phaidra.vetmeduni.ac.at/api/object/o:5100/thumbnail LOMv1.0 discipline