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Metabolism Research
08.09.2017

Immune cells help fat deal with environmental challenges

Immunosuppressive regulatory T-cells play an important role in the functioning of adipose tissue. This is the discovery of scientists from the Helmholtz Diabetes Center (HDC) at Helmholtz Zentrum München and the Technical University of Munich (TUM). Their findings are published in the journal ‘Cell Metabolism’.

Immunofluorescent staining of T cells

T cells after a short-term cold treatment (left) and under control conditions (right). Immunofluorescent staining of the T cell marker CD3 (green), the Treg marker Foxp3 (red) and the nucleus (blue). The cold treatment results in a significant increase of Foxp3 expression in T cells. Source: Helmholtz Zentrum München

The number of obese people as well as those suffering from type 2 diabetes is increasing worldwide. Both disorders are associated with metabolic changes including amplified inflammatory responses in adipose tissue. “Previous studies have indicated that immunosuppressive regulatory T-cells – or Tregs for short – play an important role in these processes”, explains the leader of the study Dr. Carolin Daniel, group leader at the Institute for Diabetes Research (IDF) of the Helmholtz Zentrum München and a scientist in the German Center for Diabetes Research (DZD).* “We now wanted to examine how these immune cells might support adipose function in more detail.”

In an experimental model, Daniel, together with co-first authors Dr. Stefanie Kälin and Maike Becker and colleagues, determined that the number of Tregs in adipose tissue increases in response to different environmental stimuli. These stimuli included a short-term cold treatment, stimulation of the sympathetic nervous system (β3-adrenoreceptors) or short-term high-caloric exposure. “All these stimuli supported those immunosuppressive cells directly in the adipose tissue”, says Becker.

Fat burning activated

The magnitude of the increase in Tregs differed depending on the type of adipose tissue: it was particularly pronounced in brown fat**, somewhat weaker in subcutaneous fat and weakest in visceral fat. To investigate the specific function of Tregs, the researchers determined how gene expression changes in adipose tissue. Especially in brown fat, genes were activated that promote heat production (thermogenesis) as well as those that are used for the breakdown (lipolysis) and burning (oxidation) of fatty acids. Subsequent experiments revealed that the signalling molecules Stat6 und Pten play a vital role in this process.

“A better understanding of the immunological mechanisms involved in the target tissue will be critical for the development of personalized interventions in order to improve adipose tissue function during obesity and diabetes”, says the leader of the study Carolin Daniel. “Our experiments show for the first time that Tregs can support fat depots in dealing with environmental challenges.”

“Our findings highlight the complex interactions between our body and the environment. We have known for a while that hormones play a key role here – but now have to accept that immune cells may be just as important for a balanced metabolism”, comments Prof. Dr. Matthias Tschöp. He is the scientific director of the HDC at Helmholtz Zentrum München and holds the chair for metabolic diseases at the TUM. “These insights therefore help us tremendously with designing more efficient ways to therapeutically optimize when and how to store calories.”

Prof. Dr. Matthias Mann from the Max Planck Institute of Biochemistry in Martinsried as well as the group of PD Dr. Benno Weigmann from Universitätsklinikum Erlangen also made significant contributions to the study.


Further Information

* Regulatory T-cells suppress unwanted immune reactions and thereby prevent autoimmune diseases, for instance. The transcription factor Foxp3, which was determined by the scientists, is characteristic for this cell type. 

** Brown adipose tissue is found in almost all mammals, including humans. Its cells produce heat by oxidizing sugars and fatty acids. This makes them an interesting target for pharmacological treatment of obesity.

Background:
The doctoral students Maike Becker, Victoria Flynn, Verena Ott, Isabelle Serr, Markus Hippich and Martin Scherm are participants in the Helmholtz Graduate School for Environmental Health (HELENA).

Original Publication:
Kälin, S. & Becker, M. et al. (2017): A Stat6/Pten axis links regulatory T cells with adipose tissue function. Cell Metabolism, DOI: 10.1016/j.cmet.2017.08.008

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. 

Technical University of Munich (TUM) is one of Europe’s leading research universities, with more than 500 professors, around 10,000 academic and non-academic staff, and 40,000 students. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, com-bined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with a campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany.  

The Institute of Diabetes Research (IDF) focuses on the pathogenesis and prevention of type 1 diabetes and type 2 diabetes and the long-term effects of gestational diabetes. A major project is the development of an insulin vaccination against type 1 diabetes. The IDF conducts long-term studies to examine the link between genes, environmental factors and the immune system for the pathogenesis of type 1 diabetes. Findings of the BABYDIAB study, which was established in 1989 as the world’s first prospective birth cohort study, identified risk genes and antibody profiles. These permit predictions to be made about the pathogenesis and onset of type 1 diabetes and will lead to changes in the classification and the time of diagnosis. The IDF 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.