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October 28, 2025npj Metabolic Health and DiseaseOpen Access

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

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Why the study?

LVH is associated with increased cardiac FGF23 expression in mice and men, but the specific role of cardiac FGF23 in LVH required further elucidation.

Does cardiomyocyte-specific deletion of Fgf23 improve cardiac metabolic health and reduce hypertrophy or fibrosis in a mouse model of pressure overload-induced LVH?

Population

Mice subjected to transverse aortic constriction and cultured cardiomyocytes

Comparison

Cardiomyocyte-specific Fgf23 knock-out vs Fgf23 fl/fl controls

Design

Preclinical animal and cell-culture experimental study

Key result

Cardiomyocyte-specific deletion of Fgf23 in mice subjected to pressure overload ameliorated hypertension and cardiac fibrosis, and induced a metabolic switch downregulating glucose consumption.

Authors

NLNejla LaticALArezou LariNSNa Sun

Discussion

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Member takes

Overview

Hypothesis-generating for cardiac FGF23 inhibition in pressure overload; leaves open human translation.

Structured PICO

Does cardiomyocyte-specific deletion of Fgf23 improve cardiac metabolic health and reduce hypertrophy or fibrosis in a mouse model of pressure overload-induced LVH?

P
Population
Mice with cardiomyocyte-specific Fgf23 knock-out (Fgf23 CKO) and Fgf23 fl/fl controls subjected to transverse aortic constriction (TAC) to induce left ventricular hypertrophy (LVH) by pressure overload, as well as cultured neonatal rat cardiomyocytes.
I
Intervention
Cardiomyocyte-specific ablation of Fgf23 (Fgf23 CKO) combined with transverse aortic constriction (TAC); in vitro treatment with recombinant FGF23.
C
Comparator
Fgf23 fl/fl mice subjected to transverse aortic constriction (TAC); vehicle treatment for in vitro cells.
O
Outcome
Development of left ventricular hypertrophy, blood pressure, cardiac fibrosis, and myocardial energy metabolism (glucose and fatty acid oxidation).surrogate

Deletion of cardiac FGF23 in a mouse model of pressure overload ameliorates hypertension and cardiac fibrosis by shifting myocardial energy metabolism from glucose consumption to fatty acid oxidation, mimicking the cardioprotective effects of SGLT2 inhibitors.

Limitations

  • Cannot distinguish endocrine from paracrine effects in cultured cardiomyocyte experiments
  • The protection against cardiac fibrosis in Fgf23 CKO TAC mice may be mediated indirectly through reduced glucose and ATP concentrations rather than a direct effect

Cite This Study

Latic et al. (2025) studied Left ventricular hypertrophy. Cardiomyocyte-specific Fgf23 deletion vs. Fgf23fl/fl control mice was evaluated on Development of left ventricular hypertrophy, cardiac fibrosis, and myocardial energy metabolism. Cardiomyocyte-specific deletion of Fgf23 in mice subjected to pressure overload ameliorated hypertension and cardiac fibrosis, and induced a metabolic switch downregulating glucose consumption.

synapsesocial.com/papers/6a11684ed2bb25adc0c311a9https://doi.org/10.1038/s44324-025-00087-w
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