RHEB and obesity due to melanocortin 4 receptor deficiency: In addition to those actions that are susceptible to developing resistance upon obesity and T2D, insulin, through the sequential PI3K-Akt activation, inhibitory phosphorylation of the complex tuberous sclerosis complex 1/2 (TSC1/TSC2), and activation of Ras homolog enriched in the brain (Rheb), activates the mechanistic target of rapamycin complex 1 (mTORC1), which in turn promotes protein synthesis by phosphorylating the ribosomal protein S6K and eukaryotic translational initiation factor 4E-binding protein 1 (4E-BP), among many other processes [18].