The present survey on the role of purinergic signaling in obesity and insulin resistance will be focused on the pleiotropic P2X7 receptor subtype (41) for its major involvement not only in the modulation of fat distribution and inflammation in white AT (42), but also in energy metabolism and nonshivering thermogenesis (39, 40). This evidence concerns the gene P2RX7 and obesity due to melanocortin 4 receptor deficiency.