Communications and Marketing

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 institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Tumour Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

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