Genetic switch for the formation of body fat discovered

Scientists from the Medical University of Vienna (MUV), together with colleagues from the IMBA and the University of Salzburg, have presented new molecular genetic findings on the origin of excess weight in people. They have been able to identify a molecular "switch" for excess weight. The work has been published in the renowned American specialist journal "Cell".

Like humans, mice have brown and white adipose tissue. Brown adipose tissue plays an important role with newborn babies, for example, because it regulates body temperature. It is found in the neck area and it burns fat and generates heat. The white adipose tissue is found everywhere in the body, in moderation it is important for storing food, for storing energy, as a "reserve". In excess it makes people sick. One example here is when it becomes stored as visceral fat in the abdominal region and causes diabetes.

As part of the project supported by the Vienna Science, Technology and Research Fund WWTF "From Flies to Humans - Novel Approaches for Obesity and Diabetes", in which genes associated with excess weight and lipometabolism are researched, Harald Esterbauer from the Department of Medical and Chemical Laboratory Diagnostics at MedUni Vienna studied genetically modified mice in which the hedgehog signal (a switch for lipometabolism) is overactive only in the fat cells. Here he discovered that activation of the hedgehog signal pathway leads to almost complete loss of white adipose tissue. "Interestingly the brown adipose tissue in this model is not affected. It also does not lead to insulin resistance and other metabolic disorders which are otherwise typically found with lipodystrophies," explains Esterbauer.

Current studies by PhD students in Esterbauer's working group are now aiming to clarify the mechanisms in detail. Using mass spectrometry Martina Bayer is attempting to further decipher the molecular processes. Sabine Amann is working on the effect of the hedgehog signal pathway in mature fat cells. She has just now been able to show that these burn more glucose after activation. In another ongoing project, Jelena Todoric (in assistant doctor training to be a laboratory physician) has managed to show for the first time that many pro-inflammatory cytokines and ligands interfere with the activation of the hedgehog signal. She also succeeded in removing the described suppression of fat cell formation via hedgehog by administering different substances which occur in the adipose tissue during inflammation. Esterbauer says on these observations: "Even if still highly speculative at the moment, it could be the case that a little inflammation in the adipose tissue may be important for the formation of additional fat cells."

Bild: Wildtyp (oben) und genetisch veränderte Maus (unten). Bei der genveränderten Maus wurde das Sufu-Gen im Fettgewebe blockiert, das hedgehog-Signal dadurch verstärkt (Abbildung: Pospisilik, IMBA)