The researchers were thus able to gain a deep insight into the function of the gene. Further clarification of its function would provide a basis for developing new approaches for prevention and treatment, as this gene could also be linked to obesity and diabetes in humans.
The researchers published their data today in the scientific journal Nature Genetics (Chadt, A. et al.; 2008).
The mutation that knocks out the Tbc1d1 gene causes increased fat uptake in skeletal muscle and, at the same time, boosts fat oxidation. On the other hand, glucose uptake of muscles is reduced. “This shows that the normal Tbc1d1 gene has a very important function in fat and glucose metabolism and therefore plays an essential role in regulation of energy metabolism“, explains Hadi Al-Hasani.
“Not only how much food we eat but also how our body uses it is decisive for development of obesity and diabetes“, says Hans-Georg Joost, Scientific Director of DIfE. When the relation between glucose and fat oxidation shifts so that the muscles use more fat and less glucose as a source of energy, this is energetically less efficient. As a result, the body stores less fat. This lowers the risk for obesity and consequently also for diabetes.
In Germany, 66 percent of the men and 50.6 percent of the women are already overweight or obese. In the USA, even three-fourths of adults “break the bathroom scales“, according to the latest reports. Overweight increases significantly the risk of heart attack, stroke, intestinal cancer, and type-2 diabetes. At present, more then seven percent of Germans are diabetic and this number will increase even more due to the growing number of overweight persons.
Studies in animals and humans have shown that there is a relation between overweight, type-2 diabetes, diet, and genes. Researchers suspect that natural variants of at least 50 genes are involved in the development of overweight. As for diabetes, probably more than 100 genes are involved. Only very few of these genes and variants are known to date. In addition, they form a functional, interacting network with environmental variables that is incompletely understood.
Since humans and mice are genetically very similar, the researchers of DIfE use the mouse model to identify genes involved in the development of overweight and diabetes. If an “overweight gene“ has been discovered which plays a role in both species, then the researchers can investigate its function and the basic molecular mechanisms in animal models under controlled conditions. Such studies often cannot be carried out in humans for ethical as well as practical reasons. The results from the animal model studies can then be used to develop new medications for treatment of obesity and diabetes.
About the study: The researchers identified the mutation on the Tbc1d1-gene by means of back-crossing experiments. Then the genetic makeup of two very different mouse strains was compared. The New Zealand obese mouse gains weight rapidly under a high-fat diet (60 percent fat) and develops obesity, whereby the proportion of body fat can increase to over 40 percent. Despite a very high fat diet, the mice of the Swiss Jim Lambert strain did not gain weight but stayed lean, due to their genetic makeup.
Seven base pairs are missing in the mutated Tbc1d1 gene of the Swiss Jim Lambert strain. These changes lead to the synthesis of a shortened Tbc1d1 protein molecule and, most likely, loss of enzyme activity. The Tbc1d1 protein molecule is located mainly in skeletal muscle. Researchers have found smaller amounts in heart, pancreas, intestine, kidney, and hypothalamus. It is not found in fatty tissue or liver.
Gisela Olias | alfa
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy