NOS3 and metabolic disease: Previous studies have shown that NR4A1 can bind to and anchor LKB1 in the nucleus, thereby inactivating the downstream AMPK signaling pathway and ultimately leading to metabolic disorders such as diabetes.[36, 38] Previous evidence suggested that inactivation of the AMPK signaling pathway can lead to oxidative stress and excessive ROS accumulation in the vascular endothelium.[39, 40] Additionally, the AMPK signaling pathway is an upstream regulator of eNOS.