Seipin Knockout Mice Develop Heart Failure With Preserved Ejection Fraction

•The lean diabetic SKO mouse represents a novel and validated murine model of HFpEF.•The SKO HFpEF mouse model recapitulates the cardiac structure and function abnormalities in lean diabetic HFpEF patients in Asia.•Altered cellular titin phosphorylation and increased extracellular interstitial fibrosis associated with neutrophil extracellular traps contribute to the left ventricular stiffness.•Metabolic disturbances arising from insulin resistance and diabetes in the absence of hypertension or obesity may lead to HFpEF.