Here we show that <i>Alms1</i> <sup>-/-</sup> (Foz/Foz) mice fed a Western diet develop MASH with advanced liver fibrosis accompanied by a HFpEF phenotype characterized by left ventricular hypertrophy, impaired cardiomyocyte contractility, reduced β-adrenergic reserve, elevated BNP, and increased mortality despite ejection fraction >50. Here, NPPB is linked to Hepatic fibrosis.