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Why 'fat gene' mutation may make you obese

“Fat-boosting gene mystery ‘solved’,” reports BBC News.

There is a wide range of existing evidence suggesting that people who have a variation in a gene called FTO are more likely to be obese. However, until now it has been unclear why this may be the case.

A new study compared men with two copies of the ‘high risk’ gene variant with men with two copies of the ‘low risk’ variant. Men with two copies of the high risk variant had less hunger suppression and less suppression of levels of the appetite stimulating hormone acyl-ghrelin after eating. In addition, brain scans found that their brains responded differently to the hormone and to pictures of food.

This interesting research suggests how the FTO variant may alter obesity risk in humans. However, these findings are unlikely to have any immediate impact on solving the obesity problem.

While it may be the case that the FTO variant could predispose people towards overeating, that is not the same thing as causing people to overeat. It may take more willpower for people with the FTO variant to stay healthy than for most people, but none of us are controlled entirely by our genes.

Eating a healthy balanced diet and taking regular exercise are more manageable ways to achieve a healthy weight. One of the easiest ways to do this is to follow the free 12-week NHS Choices weight loss guide.

Where did the story come from?

The study was carried out by researchers from the UK, Germany and Japan. It was funded by the Rosetrees Trust, University College London Hospital (UCLH) Charities, and University College London/UCLH Comprehensive Biomedical Research Centre.

The study was published in the peer-reviewed Journal of Clinical Investigation.

The research was covered well by the BBC, The Daily Telegraph and the Mail Online.

What kind of research was this?

This research combined results from studies using human participants, experiments on genetically modified mice, and from mouse and human cells cultured in the laboratory.

The researchers wanted to determine how changes (single nucleotide polymorphisms or SNPs) in the DNA sequence of the FTO gene could lead to differences in eating behaviour and obesity.

The researchers’ hypothesis was that an SNP in FTO (which has previously been linked to different eating behaviour and obesity) could impact on the levels of hormones regulating appetite.

What did the research involve?

To test their hypothesis, the researchers assessed appetite and circulating appetite hormone levels in response to a meal after an overnight fast in two groups:

  • 10 normal-weight men carrying two copies of the ‘high risk’ gene variant (rs9939609)
  • 10 normal-weight men carrying two copies of the ‘low risk’ gene variant

The men were matched for age, body mass index (BMI), fat mass and fat around the body organs. The researchers were particularly interested in the hormone acyl-ghrelin, which is an appetite stimulant.

The researchers then scanned the brains of a new group of 12 normal-weight men carrying two copies of the ‘high risk’ gene variant and 12 carrying two copies of the ‘low risk’ gene variant.

The researchers wanted to see if there were differences between the men’s brain responses to food cues, both after fasting and after a meal. To do this, the researchers used a special type of MRI scan called functional MRI (fMRI). fMRI looks at changes in blood flow in the brain and these changes are thought to be driven by increased activity in certain regions of the brain.

The researchers then performed experiments looking at expression of the FTO gene and ghrelin levels in cultured mouse and human cells, and in blood from men carrying the high risk or low risk gene variants.

What were the basic results?

After the overnight fast, and before the meal, the men carrying two copies of the high risk FTO gene variant reported similar appetite to men carrying two copies of the low risk variant. However, after the meal, men carrying the high-risk variant had less suppression of hunger than men carrying the low risk variant, and levels of acyl-ghrelin (the appetite stimulating hormone) also remained higher.

The researchers found that men carrying two copies of the high risk or low risk variant had differences in the brain response to food images. These differences occurred in areas of the brain related to reward as parts of the brain involved in what is known as ‘homeostasis’ – the body’s ability to regulate certain systems such as temperature, hunger and sleep.

Men carrying the high risk or low risk variant also had different brain responses to levels of circulating acyl-ghrelin in some regions of the brain.

Using cultured cells, and blood cells from men carrying high risk or low risk versions of the FTO gene, the researchers found that the high risk variant was associated with increased FTO expression, which leads to altered ghrelin production.   

How did the researchers interpret the results?

The researchers conclude that, “FTO regulates ghrelin, a key mediator of ingestive behaviour, and offer insight into how FTO obesity-risk alleles [genetic variations] predispose to increased energy intake and obesity in humans”.

Conclusion

Single nucleotide polymorphisms (SNPs) in the FTO gene have been linked to human obesity and obesity-prone behaviours.

This research has found that men with two copies of the high risk SNP in the FTO gene have less hunger suppression and less suppression of levels of the appetite stimulating hormone acyl-ghrelin after eating. In addition, their brains respond differently to the hormone and to pictures of food. The research also found a potential mechanism for this, as the researchers found that FTO could regulate ghrelin production.

This interesting research suggests how the FTO variant may alter obesity risk in humans. However, this was a small study and the implications of these findings are unlikely to have any immediate impact on solving the obesity problem.

While there is nothing we can do to alter our genetics, eating a healthy balanced diet and taking regular exercise are more manageable ways to achieve a healthy weight.

 

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