The role of Bergamot Polyphenolic Fraction (BPF) in MASLD-Induced HFpEF: Mitigate diastolic dysfunction by targeting chronic low-grade inflammation

Aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) is an independent risk factor and a key contributor to the pathophysiology of heart failure with preserved ejection fraction (HFpEF), highlighting the urgent need for early detection and intervention. Bioimaging techniques provide valuable morphological and functional insights to monitor the disease progression and guide therapeutic strategies targeting early metabolic and inflammatory mechanisms that link these conditions. Alongside traditional pharmacological therapies, nutraceuticals are a promising candidate for primary prevention. Here, we investigated the potential role of BPF in mitigating MASLD-related HFpEF. Methods and results: Male DIAMOND mice were randomly assigned to receive either a chow diet with tap water or a high-fat diet with sugar water. Starting at week 16, mice were further subdivided and treated with either vehicle or BPF (50 mg/kg/day po), until week 30. Echocardiographic analysis was conducted at the baseline and at week 30. Correlation and regression analyses were performed to assess the role of pro-inflammatory mediators in the onset of diastolic dysfunction. BPF supplementation ameliorated diastolic function, improving the E/A ratio, as well as left ventricular diastolic and systolic tissue strain dysfunction and dyssynchrony. These effects are induced by chronic low-grade inflammatory mediators straightly associated with the HFpEF phenotype. Conclusion: Our results demonstrated that BPF improved diastolic dysfunction and reduced chronic low-grade inflammation. Since this inflammatory state is a key predisposing factor for the HFpEF, BPF supplementation emerged as a potential therapeutic strategy to alleviate early MASLD-related inflammation and pathological changes that contribute to the onset of cardiac dysfunction.