Although nutrients can stimulate ROS production from NADPH oxidases (NOXs) and mitochondria, the inhibition of NOXs, especially NOX-2, can ameliorate several cardiovascular and metabolic diseases (Table 1), suggesting that NOXs might play a key role in translating nutrient stress into ROS signals required for initial TRPM2 activation. This evidence concerns the gene FMO5 and metabolic disease.