Adipose organ dysfunction and type 2 diabetes: Role of nitric oxide

Adipose organ, historically known as specialized lipid-handling tissue serving as the long-term fat depot, is now appreciated as the largest endocrine organ composed of two main compartments, i.e., subcutaneous and visceral adipose tissue (AT), madding up white and beige/brown adipocytes. Adipose organ dysfunction manifested as maldistribution of the compartments, hypertrophic, hypoxic, inflamed, and insulin-resistant AT, contributes to the development of type 2 diabetes (T2D). Here, we highlight the role of nitric oxide (NOGreek ano teleia) in AT (dys)function in relation to developing T2D. The key aspects determining lipid and glucose homeostasis in AT depend on the physiological levels of the NOGreek ano teleia produced via endothelial NOGreek ano teleia synthases (eNOS). In addition to decreased NOGreek ano teleia bioavailability (via decreased expression/activity of eNOS or scavenging NOGreek ano teleia), excessive NOGreek ano teleia produced by inducible NOS (iNOS) in response to hypoxia and AT inflammation may be a critical interfering factor diverting NO. signaling to the formation of reactive oxygen and nitrogen species, resulting in AT and whole -body meta- bolic dysfunction. Pharmacological approaches boosting AT -NO. availability at physiological levels (by increasing NO. production and its stability), as well as suppression of iNOS-NO. synthesis, are potential candi- dates for developing NO. -based therapeutics in T2D.