HMOX1 and obesity due to melanocortin 4 receptor deficiency: It has been suggested that in conditions associated with major cardiovascular risk factors (such as obesity, insulin resistance and metabolic syndrome), where endothelial NO production and/or bioavailability is/are decreased and oxidative stress is increased, the Nrf2/HO-1 pathway may be activated to compensate for the loss of NO bioavailability and, at least in part, preserve vascular function [38].