Importantly, the scientists found out that treatment of obese mice with this GLP-1/Glucagon co-agonist improves metabolism and body weight associated with restored function of the weight lowering hormone leptin, even in the continued presence of a high-fat, high-sugar diet. The results are published in the current issue of the official journal of the American Diabetes Association 'Diabetes'. The adipocyte hormone leptin plays a key role in the physiology of energy and glucose metabolism. Leptin is normally secreted from adipose tissue to blood in proportion to the amount of body fat. Increased leptin levels inform the brain of stored calories and it responds to inhibit food intake, increase energy expenditure and decrease blood glucose. However, obese individuals are resistant to leptin's metabolic effects, which limits the use of leptin as an anti-obesity drug. In their new study, the group of Dr. Timo Müller (Institute of Diabetes and Obesity, Helmholtz Center Munich, Germany) discovered that treatment of diet-induced obese mice with a peptide that simultaneously activates GLP-1/glucagon receptors reversed leptin resistance, improved body weight and normalized glucose metabolism even without switching to a healthier diet. "We are particularly encouraged to see that adding leptin produced weight loss beyond the benefits of the peptide-based, co-agonist" says Prof. Matthias Tschöp, Research Director of the Helmholtz Diabetes Center and Chair of Metabolic Diseases at Technische Universität München, Germany. The identification of this novel treatment strategy is the result of many years of collaboration with Ambrx and Prof. Richard DiMarchi (Indiana University) who noted: "The results are inspiring, and establish a basis for validation in human studies". Dr. Christoffer Clemmensen, the lead author of the study, adds: "If this concept proves safe and efficient at least in specific subpopulations of obese patients, then we may have come a step closer to personalized prevention of type 2 diabetes". Their findings, just published in the journal Diabetes, are aligned with the overall research objective of the Helmholtz Diabetes Center at Helmholtz Zentrum Munich, partner of the German Center for Diabetes Research (DZD). We aim to establish new approaches in the diagnosis, therapy and prevention of civilization's major diseases and to develop these approaches as quickly as possible in the context of translational research in order to provide specific benefits for society.
Further Information
Original-Publikation:
Clemmensen C, Chabenne J, Finan B, Sullivan L, Fischer K, Küchler D, Sehrer L, Ograjsek T, Hofmann S, Schriever SS, Pfluger PT, Pinkstaff J, Tschöp MH, Dimarchi R, Müller TD. GLP-1/glucagon co-agonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet. Diabetes. 2013 Dec 30. [Epub ahead of print]
As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,100 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 34,000 staff members. http://www.helmholtz-muenchen.de
The German Center for Diabetes Research (DZD) brings together experts in the field of diabetes research and interlinks basic research, epidemiology and clinical applications. Members are the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition (DIfE) in Potsdam-Rehbrücke, Helmholtz Zentrum München – German Research Center for Environmental Health, the Paul Langerhans Institutes of the University Hospital Carl Gustav Carus in Dresden and the University of Tübingen, as well as the Gottfried Wilhelm Leibniz Association and the Helmholtz Association of German Research Centres. The objective of the DZD is to find answers to open questions in diabetes research by means of a novel, integrative research approach and to make a significant contribution to improving the prevention, diagnosis and treatment of diabetes mellitus. http://www.dzd-ev.de
The Institute of Diabetes and Obesity (IDO) studies the diseases of the metabolic syndrome by means of systems biological and translational approaches on the basis of cellular systems, genetically modified mouse models and clinical intervention studies. It seeks to discover new signaling pathways in order to develop innovative therapeutic approaches for the personalized prevention and treatment of obesity, diabetes and their concomitant diseases. IDO is part of the Helmholtz Diabetes Center (HDC).
Contact for the media
Communication Department, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, 85764 Neuherberg, Germany - Phone: +49-89-3187-2238 - Fax: 089-3187-3324 - E-Mail: presse@helmholtz-muenchen.de
Scientific contact
Prof. Matthias Tschöp, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Institute of Diabetes and Obesity, Ingolstädter Landstr. 1, 85764 Neuherberg, Germany - Phone: +49-89-3187-2103 - E-Mail: matthias.tschoep@helmholtz-muenchen.de
Journal
Diabetes