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<p>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 <i>Fgf23</i> in cardiomyocytes, and employed transverse aortic constriction (TAC) to induce LVH by pressure overload. LVH developed independently of cardiac FGF23, but cardiomyocyte-specific <i>Fgf23</i> knock-out (<i>Fgf23</i><sup>CKO</sup>) TAC mice were characterized by ameliorated hypertension and a distinct reduction of cardiac fibrosis, relative to <i>Fgf23</i><sup>fl/fl</sup> TAC controls. Spatial metabolomics revealed reduced intracellular glucose abundance and lowered cardiac energy charge in <i>Fgf23</i><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 <i>Fgf23</i><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.</p><p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月28日

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  • Nejla Latic,
  • Arezou Lari,
  • Na Sun,
  • Ana Zupcic,
  • Mhaned Oubounyt,
  • Juliana Falivene,
  • Achim Buck,
  • Martin Hofer,
  • Wenhan Chang,
  • Wolfgang M. Kuebler,
  • Jan Baumbach,
  • Axel K. Walch,
  • Alexander Grabner,
  • Reinhold G. Erben

摘要

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.