TNF and obesity due to melanocortin 4 receptor deficiency: Obesity associated with overnutrition induces macrophage infiltration and chronic hypoxia, causing low-grade inflammation in the adipose tissue28 and the release of proinflammatory factors such as interleukin (IL)-1β and tumor necrosis factor α (TNF-α),29,30 thus impairing insulin signaling pathway in a number of ways.