INS and obesity due to melanocortin 4 receptor deficiency: In the following part, we will summarize the earlier work establishing the ability of cAMP to dampen mTORC1 activation in response to insulin and growth factors and then discuss our recent findings demonstrating the regulation of mTOR signaling by the PKA- and PKG-dependent signaling pathways that represent a new non-canonical pathway independent of AKT, and we will review the implications of these signaling events in cardiometabolic disease, such as obesity, non-alcoholic fatty liver disease, and cardiac remodeling.