NFE2L2 and hyperinsulinemic hypoglycemia, familial, 4: The apparent contradictory role of Nrf2 protecting mice from obesity and insulin resistance in conditions of Nrf2 deficiency in comparison to Nrf2 pharmacological activation, may be explained by the observations that Nrf2 deficiency leads to a mild increase in the levels of ROS, which stimulate the antioxidant system in a manner similar to the Nrf2 activators (reviewed in Bocci et al., 2014).