TNF and obesity due to melanocortin 4 receptor deficiency: During obesity, the expanded adipose tissues develop hypoxia and release pro-inflammatory cytokines and chemokines, leading to the infiltration of immune cells (including macrophages, natural killer cells, neutrophils, and T cells) and secretion of pro-inflammatory factors such as tumor necrosis factor (TNF), interleukin 1beta (IL-1b), and IL-6 (70–72).