Because balanced levels of NOX2 and ROS are viewed as mediators of glucose transport in muscle (134), we suggest that activation of P2X7 function may not only increase fatty acid oxidation and EE and decrease body weight, but also possibly reduce the susceptibility to insulin resistance under high-fat feeding and/or during the dysregulation of the muscle P2X7/Ca2+/ UCP3/sarcolipin-SERCA axis. The gene discussed is UCP3; the disease is Insulin resistance.