TNF and obesity due to melanocortin 4 receptor deficiency: Obesity-induced chronic inflammation and lipid accumulation impair insulin signaling pathways by promoting the secretion of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-12 (IL-12), as well as by increasing the release of free fatty acids (FFAs) from visceral adipose tissue (VAT), thereby reducing insulin sensitivity and aggravating intrahepatic lipid deposition and oxidative stress (25, 26).