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). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.