Cardiomyocyte-specific deletion of Fgf23 in mice subjected to pressure overload ameliorated hypertension and cardiac fibrosis, and induced a metabolic switch downregulating glucose consumption.
Does cardiomyocyte-specific deletion of Fgf23 improve cardiac metabolic health and reduce hypertrophy or fibrosis in a mouse model of pressure overload-induced LVH?
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.
Abstract 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 CKO ) TAC mice were characterized by ameliorated hypertension and a distinct reduction of cardiac fibrosis, relative to Fgf23 fl/fl TAC controls. Spatial metabolomics revealed reduced intracellular glucose abundance and lowered cardiac energy charge in Fgf23 CKO 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 CKO TAC mice. These findings suggest that reduced cardiac FGF23 signaling promotes cardiac metabolic health by downregulating glucose consumption and favoring fatty acid oxidation.
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.
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