Nbea gene: Heading off to get fat

19. October 2012

After a point in time some years ago when it was hoped that THE fatmaker gene would be found, scientists now assume that hundreds of genes are involved in the development of excess weight and obesity. One of these genes has now been discovered.

Body weight and the energy balance of the body are controlled by a complex interaction of neural, hormonal and metabolic processes. In the past, scientists assumed that only one gene was responsible for excess weight and obesity. We now know that several hundred genes can cause obesity. One gene has now been determined. Scientists led by Manfred Kilimann of Uppsala University in Sweden were actually tracking down the genetic cause of autism and multiple myeloma, a malignant disease of the bone marrow. Neurobeachin (NBEA) is associated in humans with these same diseases.

In order to investigate the specific impacts on mice which are lacking a copy of the neurobeachin-gene, the mice in the German Mouse Clinic, a research facility on the grounds of Helmholtz Zentrum Munich, underwent a thorough physical examination. “Scientists from Germany and many other countries cooperate with the mouse clinic in order to “discover” new and previously unknown aspects of their ‘favorite gene’ “, says Prof. Martin Hrabé de Angelis, director of the German Mouse Clinic and Professor of Genetics at the Experimental Technical University of Munich. Scientists at the German Mouse Clinic found in their studies of mice with a missing copy of the Nbea gene that these mice were heavier than their unaffected conspecifics. In detailed investigations it turned out that the higher weight was caused by a larger amount of body fat and not by increased muscle mass.

They simply eat more

Subsequently, the scientists at the mouse clinic examined in detail where the difference to the genetically modified mice resided. The mice did not prove to be couch potatoes, which was an obvious hypothesis. Also the conversion efficiency of the provided food from which energy was derived did not differ. Only an examination of the balance between the daily intake of energy via the food and the daily energy expenditure brought to light the difference: “The genetically modified mice took in an additional amount of slightly more than 3 kJ, i.e. about 0.8 kilocalories, of energy with their food!”, states Dr. Jan Rozman, scientist and Manager of the investigation unit “Energy Metabolism”.

Nevertheless, this tiny difference proved significant and reproducible and caused the young mice in one to two weeks to increase fat mass by one gram. If the two groups were fed not with normal but with a fat-rich diet, the Nbea mice after two weeks weighed about three grams more than the comparison group. Basically the same happens to them as to a person who eats more than their metabolism needs: they slowly become fat.

One reason for excess weight in humans is leptin resistance. The hormone leptin is formed mainly in the fat cells. The more fat there is in the fat cells, the higher the leptin concentration and the lower the hunger sensation. For many overweight people this important mechanism does not work: the feeling of hunger is not made to slow down. The Nbea mice were examined as to whether they react to leptin adequately. If they were infected with a dose of leptin, the animals ate less than control animals which had only received a saline solution. A leptin resistance therefore appears not to be the cause of comsuming more than the required energy.

The gene defect makes people fat as well

“Nonetheless, of what use to us humans is fat mice?”, thought the researchers to themselves and so they set out in search of NBEA in humans. They identified two common single nucleotide polymorphisms in the population, polymorphisms known as SNPs. These are individual bases which are different in the gene sequence of the NBEA gene. The gene sequence was investigated in adults and children. Here, the researchers found that the two SNPs with the catchy names rs17775456 and rs7990537 were associated with higher Body Measure Index (BMI) and higher body weight.

Whether the Nbea mouse beyond this is also suitable as a model for Autism needs to be further investigated. In conclusion, Prof. Hrabé de Angelis emphasises: “It is no coincidence that a new feature of Nbea gene was discovered, but rather the result of a clear strategy, which follows the realisation that one gene can potentially act at several points in the body and trigger different things. Systemic phenotyping, the core activity of the German Mouse Clinic, can accurately reveal these undiscovered functions, thereby creating new knowledge”.

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1 comment:

Dr Kai Rabenstein
Dr Kai Rabenstein

So glad there’s progress on the genetics front relating to obesity at long last – but it still takes far too long to get this evidence out into the mainstream of public consciousness! Most medical and paramedical staff I have ever talked to in this context still refuse to believe that there are major genetically driven differences between people in regard of basal metabolic rate and calorie handling, and consequently could not see the need for much of bariatric surgery … and had never heard of leptin.

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