Gen cause of obesity

Researchers identify a gene that makes you fat

03/14/2014

An international research team has discovered the genetic cause of obesity. The gene IRX3 plays a crucial role in the development of obesity, the scientists report to Marcelo Nóbrega from the Institute of Human Genetics at the University of Chicago in the journal „Nature“. The researchers found in experiments with mice that the rodents in the absence of IRX3 gene 25 to 30 percent less than their counterparts with active IRX3 gene.

Despite high-fat diet, the animals had not increased and they were „resistant to metabolic diseases such as diabetes and had more energy-burning cells known as brown adipose tissue“ write the scientists. In humans too, a corresponding correlation between the risk of obesity and the IRX3 gene is to be expected.

As early as 2007, several genome studies identified mutations in a gene called FTO that appeared to be associated with an increased risk of obesity and type 2 diabetes in humans. Subsequent studies confirmed the link between the gene and the body mass, so Marcelo Nóbrega and colleagues thought that this was the genetic cause of obesity. But there remained doubts, as further discrepancies arose in further investigations. Thus, the mutations had occurred in sections of the FTO gene that contained some elements that were specific to 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. Thus, subsequent studies would have revealed no link between the obesity-associated mutations and the expression of FTO, explained Marcelo Nóbrega.

Detected gene controls the energy metabolism and eating behavior and could promote obesity
Therefore, Nóbrega and colleagues expanded their search field and examined possible effects of the FTO mutations on the adjacent genes. They discovered in studies on zebrafish, mice and human cells changes in IRX3, a gene located on the genome over half a million base pairs of 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 the regulation of energy metabolism and eating behavior“, the researchers report in the journal „Nature“.

IRX3 affected by mutations of the FTO gene
Inês Barroso, geneticist at the Wellcome Trust Sanger Institute in Hinxton, UK, said in the recent article that the work of Nóbrega and colleagues answers some of the questions surrounding the discovered biological link between FTO and obesity risk. In genome-wide association studies (GWAS), there is always the problem that, while possible associations are uncovered, these are only markers on the genome that say nothing about which genes are actually affected. The current results strongly suggest that body mass is determined by IRX3 rather than FTO, Barroso continued.

Unexpected interactions between widely separated genes
Nóbrega himself stated that this example of future interactions between distant genes should be given more consideration in genetic association studies in the future. There may be many other cases where researchers study the wrong gene and virtually hunt ghosts. The scientists hope that the discovered link between the IRX3 gene and the risk of obesity will allow the development of new therapeutic approaches to obesity and obesity. (Fp)