Although it might seem counterintuitive, the oxylipin signature of the MetS participants in the Discovery study may reflect the implementation of compensatory mechanisms, including (i) the control of oxidative stress, (ii) the modulation of the CYP:sEH axis in favor of the protective epoxy-PUFAs and (iii) the production of regulatory oxylipins, such as the 15-LOX products of long-chain PUFAs to negatively regulate the 5-LOX pathway. This evidence concerns the gene EPHX2 and metabolic syndrome.