TNF and obesity due to melanocortin 4 receptor deficiency: Obesity triggers hypoxia, endoplasmic reticulum (ER) stress, and inflammatory activation of hypertrophic adipocytes, which leads to cytokines (e.g., tumor necrosis factor (TNF), interleukin-6 (IL-6)) and an altered adipokine profile (increased leptin, decreased adiponectin), resulting in systemic insulin resistance and hepatic lipogenesis [4,5,6,7,8,9].