HMGB1 released by necrotic adipocytes interacts with RAGE, inducing pro-inflammatory cytokines and ROS;S100A4, S100A8/A9, and S100B induce inflammation, interacting with RAGE;AGE accumulation in adipose tissue may contribute to obesity-associated insulin resistance. This evidence concerns the gene S100A4 and obesity due to melanocortin 4 receptor deficiency.