Nejla Latic Nejla Latic Arezou Lari Arezou Lari Na Sun Na Sun Ana Zupcic Ana Zupcic Mhaned Oubounyt Mhaned Oubounyt Juliana Falivene Juliana Falivene Achim Buck Achim Buck Martin Hofer Martin Hofer Wenhan Chang Wenhan Chang Wolfgang M. Kuebler Wolfgang M. Kuebler Jan Baumbach Jan Baumbach Axel K. Walch Axel K. Walch Alexander Grabner Alexander Grabner Reinhold G. Erben Reinhold G. Erben Springer 2025 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. PDFDocument eng 2026-05-07T08:06:47.326878Z 2025 Endocrine System And Metabolic Diseases Metabolism Metabolomics 3847214 b application/pdf http://creativecommons.org/licenses/by/4.0/