Press Release

29.09.2015

Crosslinked cellular power plants for a slim look

Our body consistently adjusts its energy management to changes in the supply of nutrients or physical activity. Malfunctioning in this process plays an essential role in the genesis of metabolic disorders like adiposity and diabetes. Scientists at the Helmholtz Zentrum München now report in the journal Cell Metabolism that in this process the protein calcineurin assumes a central function by selectively linking up mitochondria in the muscle with each other and in that way optimising cell respiration.

Pfluger, Tschöp

Dr. Paul Pfluger and Prof. Dr. Matthias Tschöp, Source: Helmholtz Zentrum München

Mitochondria transform absorbed dietary nutrients into energy. The "power plants" of the cells are joined together in a network that can be dynamically regulated by fusion or fission of mitochondria, depending on the activity and needs of the cell. Scientists at the Helmholtz Zentrum München report a new mechanism on how muscle cells utilize the formation of elongated mitochondrial nanotunnels to optimize cellular respiration and energy and glucose management throughout the entire body.

Calcineurin identified as a key molecule

Crucial in this context is the molecule calcineurin. "In our study, we could show that flies that cannot produce any calcineurin had less weight, less fat storage as well as an increased metabolic rate" says Dr Paul Pfluger from the Institute for Diabetes and Adiposity (IDO), who headed the international team of scientists from the German Centre for Diabetes Research (DZD) and the United States.

And apparently the flies are no evolutionary peculiarity: mice with a calcineurin defect were also, despite high-fat diet, protected against excessive weight and showed enhanced expenditure of calories. In order to confirm this effect, the scientists specifically inhibited the effect of calcineurin by means of an inhibitor called tacrolimus*. In actual fact, this treatment was also able to reduce weight gain from high-calorie nutrition.

Calcineurin inhibitors in the clinic for years

"A mechanism so well preserved evolutionarily for control of metabolism in flies and mice suggests that calcineurin also performs a similar function in humans," Paul Pfluger speculates. "It would therefore be an obvious conclusion to suppress the function of calcineurin through medication in order to treat obesity." Corresponding inhibitors have been deployed in high dosages in the clinic for years in order to prevent rejection reactions after tissue transplants but due to numerous side effects have not been above criticism. Effects from low-dosage calcineurin inhibitors on the body weight of adipose patients have, however, not yet been studied clinically. "In our opinion, such a study with low concentrations of calcineurin inhibitors is quite apropos. Corresponding new approaches are currently being tested," according to Pfluger.

Further information

 

Background
* Tacrolimus has for years been administered in high doses to suppress the immune system. The molecule is used with rejection reactions or atopic eczema cases. Systematic administration is however associated with numerous side effects.

Original publication:
Pfluger, P. et al. (2015). Calcineurin Links Mitochondrial Elongation with Energy Metabolism, Cell Metabolism, DOI: 10.1016/j.cmet.2015.08.022


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 2,300 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 37,000 staff members.

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).

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.

Scientific contact at Helmholtz Zentrum München:
Dr. Paul Pfluger, Helmholtz Zentrum München - German Research Center for Environmental Health (GmbH), Institute for Diabetes and Obesity, Ingolstädter Landstr. 1, 85764 Neuherberg - Phone +49 89 3187 2104 -