Together, these data implicate SMC-MR signaling as necessary for development of coronary and cardiac dysfunction in obesity and as a critical driver of obesity-associated cardiac inflammation, not only through changes in SMC but across the cardiac cellulome, supporting a role for SMC-MR in intercellular crosstalk underlying coronary and cardiac dysfunction in obesity. The gene discussed is NR3C2; the disease is obesity due to melanocortin 4 receptor deficiency.