TNF and obesity due to melanocortin 4 receptor deficiency: 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.