SFRP5 buffers non-canonical Wnt5a signaling, limiting endothelial and macrophage inflammatory activation and reducing post-ischemic myocardial inflammation; in obesity, SFRP5 levels decline while Wnt5a expression rises, shifting the vasculo-myocardial milieu toward adhesion-molecule induction, leukocyte recruitment, and fibroblast activation [44,45,46]. Here, WNT5A is linked to obesity due to melanocortin 4 receptor deficiency.