NPYY2 and Y-4 receptors selective ligands: Promising anti-obesity drugs?

Neuropeptide Y (NPY), a potent orexigen peptide widely produced and distributed in arcuate neurons in the hypothalamus, is a promising candidate for the control of appetitive ingestive behavior. In mammals, the signaling is mediated via at least five different cell surface receptors, denoted as Y-1, Y-2, Y-4 Y-5 and Y-6. Obesity is an important public health problem in the world, particularly in developed societies, and has taken on pandemic proportions. The therapeutics of obesity, including appetite suppressants, has increased 453% over the past decade, although issues concerning safety, efficacy, and little knowledge of the pharmacological activity result in the still modest effects of the anti-obesity drugs presently used. Ligands for Y receptors may be of benefit for the treatment of obesity, and recent findings have indicated a promising role of Y-2 and Y-4 in protecting against diet-induced obesity. This review highlights the supporting evidence therapeutic potential of Y-2 and Y-4 receptors antagonists as additional intervention to treat human obesity.