These investigators reported that the myocardium of both HFpEF patients and an obesity-diabetic rat model of HFpEF showed upregulation of endothelial adhesion molecules, elevated expression of the pro-oxidant protein NOX2 in macrophages and endothelial cells but not cardiomyocytes, evidence of the uncoupling of eNOS, and reduced myocardial nitrite/nitrate concentration, cGMP content, and PKG activity. Here, NOS3 is linked to obesity due to melanocortin 4 receptor deficiency.