LEP and obesity due to melanocortin 4 receptor deficiency: The interaction mechanism between obesity and CMD has been reported in previous studies indicating that adipose tissue deposition can lead to tissue hypoxia, which leads to an increase in cytokines such as leptin and interleukin-6; these adipokines and pro-inflammatory cytokines result in oxidative stress response that may lead to endothelial and microvascular dysfunction (36).