TNF and obesity due to melanocortin 4 receptor deficiency: With obesity, the macrophages in WAT stromal vascular fraction shift from an anti-inflammatory toward a pro-inflammatory phenotype, decrease the secretion of the anti-inflammatory cytokine IL-10 that enhances adipocyte insulin sensitivity, and increase the expression of inflammatory cytokines, TNFα, and IL-6, contributing to insulin resistance (Lumeng et al., 2007; Lauterbach and Wunderlich, 2017).