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Neuropeptide Y Receptor Selective Ligands in the Treatment of Obesity

Department of Gastroenterology (M.M.K.), Faculty of Medicine, University of Sao Paulo, Ribeirão Preto Campus 14048-900, Ribeirão Preto-SP, Brazil; and Department of Behavioral Medicine (A.I.), Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan

Correspondence: Address all correspondence and requests for reprints to: Akio Inui, M.D., Ph.D., Department of Behavioral Medicine, Kagoshima University Graduate School of Medicine and Dental Sciences, 8-35-1, Sakuragaoka, Kagoshima-City, 890-8520, Japan. E-mail: inui{at}m.kufm.kagoshima-u.ac.jp

Obesity is a serious public health problem throughout the world, affecting both developed societies and developing countries. The central nervous system has developed a meticulously interconnected circuitry in order to keep us fed and in an adequate nutritional state. One of these consequences is that an energy-dense environment favors the development of obesity. Neuropeptide Y (NPY) is one of the most abundant and widely distributed peptides in the central nervous system of both rodents and humans and has been implicated in a variety of physiological actions. Within the hypothalamus, NPY plays an essential role in the control of food intake and body weight. Centrally administered NPY causes robust increases in food intake and body weight and, with chronic administration, can eventually produce obesity. NPY activates a population of at least six G protein-coupled Y receptors. NPY analogs exhibit varying degrees of affinity and specificity for these Y receptors. There has been renewed speculation that ligands for Y receptors may be of benefit for the treatment of obesity. This review highlights the therapeutic potential of Y₁, Y₂, Y₄, and Y₅ receptor agonists and antagonists as additional intervention to treat human obesity.

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