PDE inhibitors: a new approach to treat metabolic syndrome?

About one third of people in the world suffer from metabolic syndrome (MetS), with symptoms such as hypertension and elevated blood cholesterol, and with increased risk of developing additional diseases such as diabetes mellitus and heart disease. The progression of this multifactorial pathology, which targets various tissues and organs, might necessitate a renewal in therapeutic approaches. Since cyclic nucleotide phosphodiesterases (PDEs), enzymes which hydrolyze cyclic AMP and cyclic GMP, play a crucial role in regulating endocrine and cardiovascular functions, inflammation, oxidative stress, and cell proliferation, all of which contribute to MetS, we wonder whether PDE inhibitors might represent new therapeutic approaches for preventing and treating MetS.

► Inflamed adipocytes secrete TNFα and angiotensin II which contribute to metabolic syndrome (MetS).
► TNFα and angio II alter cyclic nucleotide phosphodiesterases (PDE) in the cardiovascular system (CV).
► PDE5 inhibitors might restore intracellular signaling and overcome CV disease in MetS.
► PDE interactions with AMPK, Adiponectin, PPAR, and testosterone, which may decrease MetS, are discussed.
► PDE4 might interact with AMPK.
► PDE5 inhibition increases testosterone, which decreases fat in men.