Press and Public Relations

Lean despite many calories

No. 22 | 08/06/2015 | by Koh

Scientists from the German Cancer Research Center (DKFZ) have identified an enzyme in mice that is involved in obesity and metabolic disruptions associated with it, such as type 2 diabetes. When the investigators turned off the enzyme in experiments, the animals did not gain any weight despite being fed a diet that was rich in fat and caloric content. Furthermore, they did not develop diabetes. So far, however, there is still not much evidence that this mechanism also plays a role in humans.

Picture: Wikimedia Commons

Metabolism experts are increasingly convinced that obesity and many of the pathogenic changes it entails, such as Metabolic Syndrome and type 2 diabetes, are a result of chronic inflammatory processes in fatty (adipose) tissue. The adipose tissue of obese people exhibits higher-than-normal quantities of almost all types of immune and inflammatory cells.

“We are quite convinced that immune cells play a role in the pathogenic consequences of obesity,” says Professor Hans-Reimer Rodewald of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ). “But apart from that, little is understood so far about the exact processes that lead to disruptions in metabolism.” However, Rodewald’s team has now been able to take a first step towards answering this question: the researchers have identified an enzyme in immune cells that is required for metabolically linked pathogenic processes to unfold.

The enzyme, called Kit, is involved in the development of blood and immune cells, as well as stem cells. Dr. Dario Gutierrez, first author of the current publication, compared mice that had functioning Kit with animals in whose cells the enzyme had been turned off.

When the researchers fed all of the animals a fat-rich diet, the mice with Kit deficiency were protected from obesity and insulin resistance. By contrast, the mice with functioning Kit gained weight and were affected by the associated metabolic disorders.

Apart from its functions in immune cells, Kit also plays a role in many processes that are independent of the immune system. For example, it regulates liver function and impacts the central nervous system and insulin secretion. However, the DKFZ scientists showed in subsequent experiments that the culprits responsible for obesity and resulting metabolic disorders are immune cells that express Kit, not the effects that are independent of the immune system. “Now we know the key molecule involved in the development of pathogenesis. But we still have to find out which of the various immune cell types are actually involved,” says Rodewald.

The Kit enzyme is a member of the large family of receptor tyrosine kinases, for which many highly specific inhibitors have already been developed. Drugs called kinase inhibitors are used to slow down cellular growth in many cancers. Imatinib, for example, is used in the treatment of specific types of leukemia (for example, chronic myeloid leukemia, or CML) and tumors of the gastrointestinal tract. “Interestingly, a case was reported where type 2 diabetes regressed during treatment with Imatinib. This finding suggests that Kit and Metabolic Syndrome might also be linked in humans,” Rodewald hypothesized.

Dario A. Gutierrez, Sathya Muralidhar, Thorsten B. Feyerabend, Stephan Herzig and Hans-Reimer Rodewald: Hematopoietic Kit deficiency, rather than lack of mast cells, protects mice from obesity and insulin resistance. Cell Metabolism 2015, DOI: 10.1016/j.cmet.2015.04.013

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.

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