Genetically responsible for obesity

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Researchers identify a gene that makes you fat

An international team of researchers has discovered the genetic cause of obesity. The IRX3 gene plays a major role in the development of obesity, the scientists around Marcelo Nóbrega from the Institute of Human Genetics at the University of Chicago report in the journal "Nature". In experiments with mice, the researchers found that rodents who were missing the IRX3 gene weighed 25 to 30 percent less than their counterparts with an active IRX3 gene.

Despite the high-fat diet, the animals did not gain weight and they were also "resistant to metabolic diseases such as diabetes and had more energy-burning cells, known as brown adipose tissue", the scientists write. A corresponding connection between the risk of obesity and the IRX3 gene can also be expected in humans.

As early as 2007, several genome studies identified mutations in a gene called FTO that appeared to be strongly related to an increased risk of obesity and type 2 diabetes in humans. In the subsequent studies, the link between the gene and body mass could be confirmed, so Marcelo Nóbrega and colleagues thought that this was the genetic cause of obesity. However, doubts remained as there were some discrepancies in further investigations. The mutations occurred in sections of the FTO gene that contained some elements that were specific for the regulation of lung tissue - "one of the few tissues in which FTO is not expressed," the scientists report. But this was not the only red flag. Subsequent studies would have shown no link between the obesity-associated mutations and the expression of FTO, explained Marcelo Nóbrega.

Discovered gene controls energy metabolism and eating behavior and could promote obesity. Therefore, Nóbrega and colleagues expanded their search field and examined the possible effects of the FTO mutations on the adjacent genes. In studies on zebrafish, mice and human cells, they discovered changes in IRX3, a gene that is located on the genome over half a million base pairs away from FTO. "IRX3 encodes a transcription factor that determines the expression of other genes and is strongly represented in the brain, where it plays an important role in regulating energy metabolism and eating behavior," the researchers report in the journal "Nature".

IRX3 affected by mutations in the FTO gene Inês Barroso, a geneticist at the Wellcome Trust Sanger Institute in Hinxton (Great Britain), emphasized in the current article that the work of Nóbrega and colleagues addresses some of the questions surrounding the discovered biological link between FTO and the risk of obesity answer. The problem with genome-wide association studies (GWAS) is always that possible associations are uncovered, but these are only markers on the genome that do not say anything about which genes are actually affected. The current results strongly indicate that the body mass is determined by IRX3 and not by FTO, continues Barroso.

Unexpected interactions between widely spaced genes Nóbrega himself explained that this example of unexpected interactions between distant genes should be given greater consideration in future genetic association studies. There could be many other cases in which researchers study the wrong gene and virtually hunt ghosts. The scientists hope that the relationship between the IRX3 gene and the risk of obesity will enable the development of new therapeutic approaches against obesity and obesity. (fp)

Image: Gerd Altmann /

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Video: Obesity: Its More Complex than You Think. Fatima Cody Stanford. Radcliffe Institute

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