In view of the role of cAMP intracellular levels in the regulation of adipogenic and lipolytic processes driven by PGE2 metabolism, and the pivotal role of PTGE-2 in obesity-related disorders, we investigated the involvement of PTGES-2 in the expression of EPAC2, known as a cAMP effector and recently associated with ST2/IL-33 mechanosensitive system involved in the maladaptive heart response. This evidence concerns the gene RAPGEF4 and obesity due to melanocortin 4 receptor deficiency.