Retinol-binding protein 4 (RBP4), elevated in obesity and HFpEF [54], is produced by EAT and drives a harmful cycle of insulin resistance and inflammation through activation of the TLR-4 pathway, fostering ROS production, cardiomyocyte hypertrophy, and reduced glucose uptake, thereby impairing cardiac metabolism and efficiency [68]. This evidence concerns the gene RBP4 and obesity due to melanocortin 4 receptor deficiency.