Page URL:

There's a new 'fat gene' in town...

17 March 2014
Appeared in BioNews 746

Scientists have identified a gene called IRX3 which is associated with obesity and may emerge as a serious contender as the most important 'fat gene' yet discovered.

The popular term 'fat gene' refers to genetic markers that are strongly linked to obesity, and they are mostly discovered thanks to genome-wide association studies (GWAS). To date, the strongest association has been found with markers in the FTO gene, and studies have sought to understand the role FTO plays in obesity.

Now a study in the journal Nature has shown that the genetic markers in the FTO gene actually regulate the expression of another gene, IRX3.

'Our data strongly suggest that IRX3 controls body mass and regulates body composition', said senior author Dr Marcelo Nobrega from the University of Chicago. 'Any association between FTO and obesity appears due to the influence of IRX3'.

It was already recognised that the genetic markers in the FTO gene are found in 'non-coding' regions of the gene and so not associated with the function of the gene itself.

Dr Nobrega's team were trying to understand why this should be so. This led to a hunt for other genes that could be regulated by the obesity-linked FTO markers and IRX3 emerged as the most likely candidate.

Although IRX3 is half-a-million base-pairs away from FTO on the genome, 'the switches that control IRX3 are [...] actually inside the FTO gene', Dr Nobrega said.

The researchers also investigated whether the IRX3 gene was directly related to obesity by genetically engineering mice without the IRX3 gene. These mice were leaner than mice with a functioning IRX3 gene, weighed 25 to 30 percent less and did not gain weight even on a high-fat diet.

'These mice are thin. They lose weight primarily through the loss of fat. But they are not runts', said co-author Dr Chin-Chung Hui, from the University of Toronto. 'They are also completely resistant to high-fat diet-induced obesity. They have much better ability to handle glucose, and seem protected against diabetes'.

The investigators saw similar results when IRX3 function was altered in the hypothalamus area of the brain, suggesting that area as important to how the gene influences body mass.

But fully understanding how IRX3 operates will be a complex task. IRX3 encodes a protein that regulates the expression of other genes and the next step for researchers will be to identify these.

'IRX3 is probably a master regulator of genetic programs in the cells where it is expressed', Dr Nobrega said. 'We're interested in what its targets are and what they alter. The goal is to identify downstream targets of IRX3 that become models for drug targeting'.

Discussing the study in Nature magazine, Dr Inês Barroso, head of human genetics at the Wellcome Trust Sanger Institute, who was not involved in the study, said: 'That's always the tricky thing; a GWAS gives you an association, but it's just a marker on the genome, it doesn't actually say anything about which gene it's affecting'.

'This [study] strongly suggests that mediation of body mass is going to be through IRX3 rather than FTO'.

Do YOU have the 'fat gene'? Discovery of protein that controls metabolism could lead to anti-obesity drug
Daily Mail |  12 March 2014
IRX3 is likely the 'fat gene'
EurekAlert! (press release) |  12 March 2014
New contender for 'fat gene' found
Nature |  12 March 2014
Obesity-associated variants within FTO form long-range functional connections with IRX3
Nature |  12 March 2014
Researchers Claim Discovery of THE 'Fat Gene'
Genetic Engineering and Biotechnology News |  13 March 2014
Scientists home in on the real 'fat gene'
Los Angeles Times |  13 March 2014
7 June 2021 - by Devika Sooklall 
Obesity may be caused by a mutation in our genes and not just our environment...
10 October 2016 - by Dr Marianne Kennedy 
Scientists at Cambridge University have shown a genetic variant increases a person's preference for high fat food...
7 September 2015 - by Dr James Heather 
Recent findings linking the FTO gene to adipose cell energy use not only revealed a molecular mechanism that contributes to obesity, but they are also an exemplar of how genome-wide association study findings can make the journey to clinical relevance...
24 August 2015 - by Dr James Heather 
Researchers have discovered the mechanism that links variations in the so-called 'obesity gene' FTO to weight gain...
16 February 2015 - by Kirsty Oswald 
A meta-analysis has found that around a fifth of variation in BMI is due to common genetic variation...
10 March 2014 - by Dr James Heather 
The media likes to push the idea that the obesity epidemic is fuelled entirely by our increasingly well-fed and sedentary lives, which makes the opportunity to hear solid evidence for the other side of the equation refreshing...
22 July 2013 - by Julianna Photopoulos 
A gene known to be linked to a much higher risk of obesity has been found to affect levels of the hunger hormone ghrelin, according to an international group of scientists...
11 March 2013 - by George Frodsham 
Scientists have found a link between skin cancer and the FTO gene, which was already associated with obesity...
26 November 2012 - by Dr Nicola Davis 
A gene linked to obesity may also provide protection from major depression, say scientists...
to add a Comment.

By posting a comment you agree to abide by the BioNews terms and conditions

Syndicate this story - click here to enquire about using this story.