In metabolic and cardiovascular disease, including diabetes, obesity, and atherosclerosis, inflammatory signaling through the inhibitor of nuclear factor-kβ kinase (IKKβ) in response to cytokines and elevated free fatty acids (FFA) levels induces insulin resistance in both vascular endothelium and metabolic targets of insulin, such as the skeletal muscle [38,39] (Figure 4). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.