Y2, Y4 receptors and obesity

Abstract

The neuropeptide Y system – comprising neuropeptide Y, peptide YY, pancreatic polypeptide and the Y receptors through which they act (Y1, Y2, Y4, Y5 and y6) – has been at the center of attention with regards to regulation of feeding behavior and its possible involvement in obesity. In the past, research has focused mainly on the orexigenic and obesogenic action of this system, with Y1 and Y5 receptors being prime candidates as mediators of neuropeptide Y-induced hyperphagia and obesity. However, in recent years, the role of other members of the neuropeptide Y family, peptide YY, pancreatic polypeptide and the Y2 and Y4 receptors through which they predominantly act, have commanded increasing attention on account of their effects to mediate satiety and promote weight loss via actions in key brain structures, such as the arcuate nucleus of the hypothalamus and the brain stem. This review focuses on the role of peptide YY- and pancreatic polypeptide-like compounds as possible antiobesity drugs, taking into account their effects, not only on energy balance, but also in the regulation of bone formation, and highlights potential benefits of using Y2 and/or Y4 antagonists (as opposed to agonists such as peptide YY or pancreatic polypeptide) in the treatment of obesity.