While we recognize the complexity of interacting systems in animals and that much more work is needed to comprehensively understand the full extent of interorgan communication, our study investigates the previously unknown systemic effects of cardiac deletion of METTL3 and opens the door to understanding the role of the cardiac secretome in the background of diet-induced obesity. This evidence concerns the gene METTL3 and obesity due to melanocortin 4 receptor deficiency.