Moreover, it has been demonstrated that improving endothelial function could ameliorate insulin resistance, whereas improving insulin sensitivity could ameliorate endothelial dysfunction, which suggesting the reciprocal relationships between insulin resistance and endothelial dysfunction.58 Endothelial dysfunction has been identified as the primary and a crucial step of the development of atherosclerosis.52, 59, 60 In addition, inflammation plays an important role in this process, which is also the common disease feature of obesity, insulin resistance and endothelial dysfunction. This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.