Phosphodiesterase: insight from molecular targets for glycolipid metabolism

Glycolipid metabolism is a crucial physiological process that provides both energy and essential biomaterials for the body. Maintaining homeostasis and precise regulatory control is vital for sustaining overall health. With shifts in lifestyle and nutritional habits, the incidence of major metabolic disorders characterized by dysregulation of glucose and lipid metabolism-such as diabetes, fatty liver disease, obesity, atherosclerosis, and cardiovascular disease-has increased steadily in recent years. Consequently, elucidating the physiological mechanisms underlying glucose and lipid metabolism, as well as identifying novel therapeutic targets for metabolic diseases, has become a major research focus. Phosphodiesterases (PDEs) have emerged as promising targets for modulating glucose and lipid metabolism by regulating intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling pathways. This review summarizes the molecular structure, subcellular localization, and signaling mechanisms of PDEs involved in the regulation of glucose and lipid metabolism and energy homeostasis. Furthermore, it highlights recent advances in the development and pharmacological evaluation of PDE inhibitors in animal models of metabolic disorders. Emphasis is placed on the roles of PDE inhibition in modulating metabolic pathways, providing a theoretical foundation for the development of potential therapeutics targeting glucose- and lipid-related metabolic diseases.