Adiponectin is the most abundant protein secreted by adipose tissue and exhibits potent anti-inflammatory properties.138 In contrast to other adipokines, plasma adiponectin levels were reduced by pro-inflammatory factors like TNF-α, IL-6, ROS, and hypoxia in animal models of obesity and IR.139,140 Adiponectin activates the AMPK and PPAR-α signaling pathways through adiponectin receptor 1 (AdipoR1) and AdipoR2 respectively, leading to enhanced fatty acid oxidation and glucose uptake in muscle, along with suppressed gluconeogenesis in liver tissues. This evidence concerns the gene PPARA and obesity due to melanocortin 4 receptor deficiency.