Tissue-specific regulation (such as differential activation of EPAC/PKA) and downstream effects (such as adiponectin secretion, inflammatory factor regulation, and enhanced thermogenesis) provide a multitarget intervention approach for obesity treatment, whereas the development of PDE inhibitors holds promise as a new direction for improving metabolic disorders. This evidence concerns the gene RAPGEF4 and obesity due to melanocortin 4 receptor deficiency.