Host: The Japanese Society of Toxicology
Name : The 51st Annual Meeting of the Japanese Society of Toxicology
Date : July 03, 2024 - July 05, 2024
Background
Non-alcoholic steatohepatitis (NASH) is defined by hepatic fat accumulation, inflammation, and fibrosis. NASH commonly coexists with hypertrophic cardiomyopathy, and its etiology is often attributed to elevated afterload due to reduced hepatic blood flow. However, limited studies suggest that augmented circulating factors linked to NASH may directly impact cardiomyocytes, potentially contributing to myocardial hypertrophy. Fibroblast growth factor 23 (FGF23) has recently emerged as a potential inducer of myocardial hypertrophy. Here, we examined if serum FGF23 levels rise in NASH and FGF23 contributes to myocardial hypertrophy in vivo.
Methods and Results
C57BL/6J mice were fed a high-fat diet (60 kcal% fat, choline deficiency, reduced methionine) for 12 weeks to induce NASH. Hypertrophy was assessed by heart weight/body weight ratio, left ventricular wall thickness, myocardial fiber thickness, and mRNA expression of hypertrophy markers (Anp, Bnp). Serum FGF23 levels were measured by ELISA. NASH mice showed elevated hypertrophy parameters and serum FGF23 levels compared to control mice. Moreover, continuous FGF23 administration (30μg/kg/day for 7 days) increased serum FGF23 levels as expected, and the hypertrophy parameters were also significantly increased.
Conclusion
This study shows the presence of myocardial hypertrophy in NASH accompanied by elevated serum FGF23 levels. Furthermore, continuous FGF23 administration induces myocardial hypertrophy. These findings indicate a potential mechanism whereby hypertrophic cardiomyopathy in NASH may involve FGF23 elevation alongside established mechanical pathways.
