INS and obesity due to melanocortin 4 receptor deficiency: Importantly, increased NOX4-ROS in AT due to obesity promote the generation of dysregulated metabolism through increased production of adipokines such as plasminogen activator inhibitor 1 (PAI-1), IL-6, and monocyte chemotactic protein-1, and decreases the generation of the insulin-sensitizing factor, adiponectin (Furukawa et al., 2004).