Biased signaling: A viable strategy to drug ghrelin receptors for the treatment of obesity |
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| Institution: | 1. Department of Pharmacology and Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA;2. Institute for Medical Physics and Biophysics, Medical Department, Leipzig University, Härtelstrasse 16-18, 04107 Leipzig, Germany;3. Institute of Biochemistry, Faculty of Life Sciences, Leipzig University, Brüderstrasse 34, 04103 Leipzig, Germany;1. Dept. of Medical, Surgical and Health Sciences – University of Trieste, Italy and Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), Trieste, Italy;2. Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, MN, USA;1. Departments of Internal Medicine (Divisions of Hypothalamic Research and Endocrinology and Metabolism) and Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, 75390-9077, USA;2. The Saban Research Institute, Developmental Neuroscience Program, Children''s Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA;3. Inserm, Jean-Pierre Aubert Research Center, U1172, University Lille 2, Lille, 59045, France;4. Metabolic Disease and Obesity Theme, Biomedicine Discovery Institute, Department of Physiology, Monash University, Clayton, Victoria 3183, Australia;1. Departments of Pathology, Chemistry, Medical Imaging, Medical Biophysics, and Oncology, Western University, Richmond Street, London, Ontario, Canada;2. Imaging Program, Lawson Health Research Institute, 268 Grosvenor Street, London, Ontario N6A 4V2, Canada |
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| Abstract: | Obesity is a global burden and a chronic ailment with damaging overall health effects. Ghrelin, an octanoylated 28 amino acid peptide hormone, is secreted from the oxyntic mucosa of the stomach. Ghrelin acts on regions of the hypothalamus to regulate feeding behavior and glucose homeostasis through its G protein-coupled receptor. Recently, several central pathways modulating the metabolic actions of ghrelin have been reported. While these signaling pathways can be inhibited or activated by antagonists or agonists, they can also be discriminatingly activated in a “biased” response to impart different degrees of activation in distinct pathways downstream of the receptor. Here, we review recent ghrelin biased signaling findings as well as characteristics of ghrelin hormone and its receptors pertinent for biased signaling. We then evaluate the feasibility for ghrelin receptor biased signaling as a strategy for the development of effective pharmacotherapy in obesity treatment. |
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