In the context of obesity, which is common in patients at risk of type 2 DM, IRresults from increased levels of free fatty acids (FFAs), and the FFAby-products pro-inflammatory cytokines and diacylglycerols (DAG), that inhibitphosphorylation of the insulin receptor substrate 1 (IRS-1) in phosphorylationdomains (serine/threonine), preventing the propagation of signals to thetranslocation of the glucose transporter-4 (GLUT4) translocation to the plasmamembrane. Here, IRS1 is linked to obesity due to melanocortin 4 receptor deficiency.