In obesity conditions, HMGB1 released by necrotic adipocytes interacts with RAGE, inducing the secretion of proinflammatory cytokines, and recruits immune cells that in turn induce additional adipocyte death through the further release of proinflammatory cytokines and ROS production [60]. This evidence concerns the gene HMGB1 and obesity due to melanocortin 4 receptor deficiency.