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 (Fgf23<sup>CKO</sup>) TAC mice were characterized by ameliorated hypertension and a distinct reduction of cardiac fibrosis, relative to Fgf23<sup>fl/fl</sup> TAC controls. Spatial metabolomics revealed reduced intracellular glucose abundance and lowered cardiac energy charge in Fgf23<sup>CKO</sup> 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 Fgf23<sup>CKO</sup> TAC mice. These findings suggest that reduced cardiac FGF23 signaling promotes cardiac metabolic health by downregulating glucose consumption and favoring fatty acid oxidation. Created in https://BioRender.com.
Authors
- Wenhan Chang (ORCID: https://orcid.org/0000-0001-6583-7176)
- Nejla Latic (ORCID: https://orcid.org/0000-0001-5635-5175)
- Mhaned Oubounyt (ORCID: https://orcid.org/0000-0001-5011-6683)
- Arezou Lari (ORCID: https://orcid.org/0000-0003-4057-7421)
- Wolfgang M. Kuebler (ORCID: https://orcid.org/0000-0003-4100-2961)
- Reinhold G. Erben (ORCID: https://orcid.org/0000-0003-0801-6958)
- Juliana Falivene (ORCID: https://orcid.org/0000-0003-3437-4863)
- Achim Buck (ORCID: https://orcid.org/0000-0001-9135-9032)
- Alexander Grabner (ORCID: https://orcid.org/0000-0002-5544-1896)
- Ana Zupcic
- Jan Baumbach (ORCID: https://orcid.org/0000-0002-0282-0462)
- Axel Walch (ORCID: https://orcid.org/0000-0001-5578-4023)
- Martin Hofer
- Na Sun (ORCID: https://orcid.org/0009-0005-1012-1687)
Institutions
- San Francisco VA Medical Center (US)
- University of Veterinary Medicine Vienna (AT)
- Universität Hamburg (DE)
- University of California San Francisco Medical Center (US)
- Duke Medical Center (US)
- Institute of Groundwater Ecology (DE)
- Ludwig Boltzmann Institute of Osteology (AT)
- Ludwig Boltzmann Institute for Cancer Research (AT)
- Charité - Universitätsmedizin Berlin (DE)
Publication Details
- Journal
- npj Metabolic Health and Disease
- Published
- 2025-10-28
- DOI
- https://doi.org/10.1038/s44324-025-00087-w
- Citations
- 2
- Primary Topic
- Fibroblast Growth Factor Research
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- Deutsche Forschungsgemeinschaft
- Austrian Science Fund
- Universität Wien
- Medizinische Universität Wien
- Veterinärmedizinische Universität Wien