The growing number of overweight people has long been one of modern society’s pressing issues. In particular the resulting metabolic diseases such as type 2 diabetes and corresponding secondary conditions can have serious consequences for health. A reduced intake of calories, such as in the framework of an intermittent fasting diet, can help to whip the metabolism back into shape – but why does this happen?
This is the question that Prof. Dr. Stephan Herzig, Director of the Institute for Diabetes and Cancer (IDC) at the Helmholtz Zentrum München, and Dr. Adam J. Rose, head of the ‚Protein metabolism in health and disease‘ research group at the DKFZ in Heidelberg, wanted to answer. „Once we understand how fasting influences our metabolism we can attempt to bring about this effect therapeutically,“ Herzig states.
Stress molecule reduces the absorption of fatty acids in the liver
In the current study, the scientists looked for liver cell genetic activity differences that were caused by fasting. With the help of so-called transcript arrays, they were able to show that especially the gene for the protein GADD45β was often read differently depending on the diet: the greater the hunger, the more frequently the cells produced the molecule, whose name stands for ‚Growth Arrest and DNA Damage-inducible‘. As the name says, the molecule was previously associated with the repair of damage to the genetic information and the cell cycle, rather than with metabolic biology.
Subsequent simulation tests showed that GADD45β is responsible for controlling the absorption of fatty acids in the liver. Mice who lacked the corresponding gene were more likely to develop fatty liver disease. However when the protein was restored, the fat content of the liver normalized and also sugar metabolism improved. The scientists were able to confirm the result also in humans: a low GADD45β level was accompanied by increased fat accumulation in the liver and an elevated blood sugar level.
„The stress on the liver cells caused by fasting consequently appears to stimulate GADD45β production, which then adjusts the metabolism to the low food intake,“ Herzig summarizes. The researchers now want to use the new findings for therapeutic intervention in the fat and sugar metabolism so that the positive effects of food deprivation might be translated for treatment.
* Researchers at the Deutsches Institut für Ernährungsforschung in Potsdam-Rehbrücke (German Institute of Human Nutrition – DIfE), also a DZD member, already made similar observations a year ago (http://www.dife.de/presse/pressemitteilungen/?id=1302). They also succeeded in detecting a change in the liver’s fat content and a reduction in particularly the quantity of those fats suspected of promoting insulin resistance. They attributed this to a modified composition of the protein molecules bound to the fat droplets. Improved energy metabolism was also observed as a result of the fasting. Further examinations are necessary, however, in order to further explain this molecular correlation. This was the starting point of the current study by Prof. Herzig’s team.
Fuhrmeister, J. et al. (2016). Fasting-induced liver GADD45β restrains hepatic fatty acid uptake and improves metabolic health, EMBO Molecular Medicine, DOI: 10.15252/emmm.201505801
The Helmholtz Zentrum München, the German Research Center for Environmental Health, pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München is headquartered in Neuherberg in the north of Munich and has about 2,300 staff members. It is a member of the Helmholtz Association, a community of 18 scientific-technical and medical-biological research centers with a total of about 37,000 staff members.
The Institute for Diabetes and Cancer (IDC) is a member of the Helmholtz Diabetes Center (HDC) at the Helmholtz Center Munich and also a partner within the Joint Heidelberg-IDC Translational Diabetes Program. The Institute for Diabetes and Cancer is tightly integrated into the German Center for Diabetes Research (DZD) and the Collaborative Research Center SFB 1118 “Reactive metabolites and diabetic complications” at the University Medicine Heidelberg, Germany. The IDC is investigating the molecular basis of severe metabolic disorders, including the Metabolic Syndrome and Type 2 Diabetes, and their roles in tumor initiation and progression.
The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich.
The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institute in Germany. At DKFZ, more than 1,000 scientists investigate how cancer develops, identify cancer risk factors and endeavor to find new strategies to prevent people from getting cancer. They develop novel approaches to make tumor diagnosis more precise and treatment of cancer patients more successful. The staff of the Cancer Information Service (KID) offers information about the widespread disease of cancer for patients, their families, and the general public. Jointly with Heidelberg University Hospital, DKFZ has established the National Center for Tumor Diseases (NCT) Heidelberg, where promising approaches from cancer research are translated into the clinic. In the German Consortium for Translational Cancer Research (DKTK), one of six German Centers for Health Research, DKFZ maintains translational centers at seven university partnering sites. Combining excellent university hospitals with high-profile research at a Helmholtz Center is an important contribution to improving the chances of cancer patients. DKFZ is a member of the Helmholtz Association of National Research Centers, with ninety percent of its funding coming from the German Federal Ministry of Education and Research and the remaining ten percent from the State of Baden-Württemberg.