NPR3 and obesity due to melanocortin 4 receptor deficiency: In fact, the previous studies showed that the downregulation of NPR-A expression and upregulation of NP degradation systems (i.e., NP clearance receptor [NPR-C] and neprilysin) are observed in obese or diabetic subjects27,41,42, which may result in the blunted impact of NPs on obesity.