The activity of certain isoforms of NADPH oxidase is inhibited by anti-oxidant adipokines such as adiponectin and omentin-1 [29,35] but promoted by pro-oxidative adipokines such as leptin, resistin, and subsequent insulin resistance, which contributes to a pro-oxidative state, endothelial dysfunction, and accelerated biological senescence [36,37,38], with the adiponectin to leptin ratio being a promising index to estimate the obesity-associated cardiometabolic risk [39,40]. Here, RETN is linked to obesity due to melanocortin 4 receptor deficiency.