Animal models for diet-induced obesity (49, 50), pre-diabetes (51), T2D (52–55), and lipotoxic cardiomyopathy (56) conclusively showed upregulation of vascular adhesion molecules [e.g., intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1] and infiltration of macrophages into the heart—a phenomenon similarly observed in obese patients with HFpEF (10, 57). Here, ICAM1 is linked to obesity due to melanocortin 4 receptor deficiency.