Mount Sinai Researchers Identify New Receptor in Brain Important for Controlling Obesity
Lab of Lakshmi A. Devi, PhD, uses mouse model to locate the receptor.
A receptor in the brain's feeding center, important in obesity and other eating disorders, has been identified by researchers at the Icahn School of Medicine at Mount Sinai. Researchers muted the receptor in the feeding center of the brain in a mouse model to show that activation of the receptor influences food intake. When investigators silenced the receptor, the mouse stopped feeding. The findings, published online in the journal Proceedings of the National Academy of Science [http://www.pnas.org/content/early/2013/09/13/1312938110.long link], provide a new direction for developing therapies to control both obesity and anorexia.
Researchers were able to show that the newly-identified receptor (GPR171) is important for controlling feeding and body weight, suggesting that discovery of the receptor system may lead to new drug targets for obesity and weight management disorders.
"The regulation of body weight involves a variety of factors, each of which has been a major breakthrough when published," said the study's lead investigator, Lakshmi A. Devi, PhD, Professor, Dorothy H. and Lewis Rosenstiel Departments of Pharmacology and Systems Therapeutics, Neuroscience, and Psychiatry, at the Icahn School of Medicine at Mount Sinai. She explained further: "The pathways that we have known about until now, that are important in regulating hunger and satiety, do not explain how animals regulate body weight. What we describe in this manuscript is a ‘missing link' -- an entirely new receptor system."
Obesity is a major public health problem in the US and around the world. A recent study by the Centers for Disease Control and Prevention (CDC) projected that by 2030, 42 percent of Americans will be obese. As the population of obese people increases, so does the projected healthcare cost of their treatment, expected to cost $549.5 billion over the next two decades, according to the CDC.
Dr. Devi also pointed out that tackling obesity with diet, exercise, and previously-developed drugs has not proven effective. "We have no doubt that new drugs and drug targets will be essential for battling this issue," said Dr. Devi.
Toward that end, Dr. Devi's laboratory is in the process of working with drugs that show promise in targeting the receptor. This study provides the proof of principle that will lead to research and development into new drugs that target GPR171. In fact, drugs could work not only for obesity, but for feeding disorders, such as anorexia.
Other contributors to this research at the Icahn School of Medicine at Mount Sinai included Ivone Gomes, PhD and Associate Professor; Achla Gupta, PhD and Assistant Professor; Jonathan Wardman, PhD and a Postdoctoral Fellow; and Khatuna Gagnidgze, PhD, a Postdoctoral Fellow; and all members of the Devi Laboratory in the Department of Pharmacology and Systems Therapeutics. William Wetsel, PhD, from Duke University, also contributed to this work, conducting studies to evaluate the metabolic changes in mice with reduced receptor levels.
This research was made possible with grants from the National Institutes on Drug Abuse and National Institute of Neurological Sciences of the National Institutes of Health.
About the Department of Pharmacology and Systems Therapeutics
The Dorothy H. and Lewis Rosenstiel Department of Pharmacology and Systems Therapeutics at the Icahn School of Medicine at Mount Sinai is devoted to the study of biological processes at molecular, cellular, tissue, and organismal levels in order to understand the mechanisms by which these processes function and how these processes can be modulated for therapeutic purposes. Studies often involve analysis of interactions of exogenous and endogenous substances with biological systems and the development of new therapeutics based on our understanding of cellular and molecular interactions.
About The Mount Sinai Medical Center
The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Icahn School of Medicine at Mount Sinai. Established in 1968, the Icahn School of Medicine is one of the leading medical schools in the United States, with more than 3,400 faculty in 32 departments and 14 research institutes. It ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by U.S. News & World Report. The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. The Mount Sinai Hospital is nationally ranked by U.S. News & World Report as one of the top 25 hospitals in 7 specialties based on reputation, safety, and other patient-care factors.