TNF and obesity due to melanocortin 4 receptor deficiency: In obesity, insulin resistance and T2D, PA-induced activation of monocyte/macrophages enhances the production of inflammatory cytokines like tumor necrosis factor-alpha (TNF-α) and Interleukin (IL)-1β, and dysregulates key macrophage functions implicated in inflammatory cardiometabolic diseases (7, 8, 9).