Obesity

'Obesity gene' probed further

Research into a “fat gene” may lead to a new anti-obesity pill, The Daily Telegraph has reported. The newspaper said mice that carried extra copies of a gene called Fto “ate more and became fatter than normal mice”.

Researchers were prompted to look at the Fto gene because variations in this gene have previously been linked to obesity in human studies. Both genetic and environmental factors are likely to have an effect on obesity, and studies such as this may partially explain why some people are more prone to gaining weight than others.

However, this study does not suggest that people carrying the ‘at risk’ genetic variations in the human form of the Fto gene cannot maintain a healthy weight or that they cannot lose weight by reducing food intake or increasing physical activity. It is too early to say whether this research may contribute to the development of new anti-obesity drugs in the future.

Where did the story come from?

The study was carried out by researchers from Medical Research Council Harwell and other research centres in the UK and Germany, and was funded by the Wellcome Trust. It was published in the peer-reviewed scientific journal Nature Genetics.

The Daily Telegraph, The Independent, and Daily Mail have all covered this study. All of the papers mention the possibility of new anti-obesity drugs in a measured way. The study does not support the Daily Mail’s headline that suggests your diet may be “doomed before you even start”.

What kind of research was this?

This was animal research looking at the effects of the Fto gene on weight and appetite in mice. Genome-wide association studies in humans have found that single ‘letter’ variations in the genetic code within the DNA of the Fto gene are associated with an increased risk of obesity. Humans who carry two copies of the ‘at risk’ form of one of the variations, called rs9939609, on average weigh 3kg more than people who carry two copies of the ‘low risk’ variation. Previous human and animal studies have suggested that this form of the gene may be more active, which may be the cause of this extra weight.

To investigate this, the researchers wanted to test whether making the Fto gene more active in mice might cause them to become obese.

The methods used in this study were an appropriate way to investigate whether the genetic variations identified in human studies could cause obesity. Ethical and safety issues mean such research would obviously not be possible in humans.

What did the research involve?

The researchers genetically engineered mice to carry one or two extra copies of the Fto gene. Carrying these extra copies of the gene would mean that these mice could produce more of the Fto protein than a normal mouse.

The researchers compared the weight, fat mass, activity levels, and food consumption of genetically engineered and normal mice over time. They also looked at the effects of feeding the mice using different diets – a normal diet and a high-fat diet.

What were the basic results?

The researchers found that in the genetically engineered mice carrying one or two extra copies of the Fto gene, these genes were sending more ‘messages’ to the cell to produce Fto protein than in normal mice.

Mice carrying extra copies of the Fto gene also weighed more than normal mice. At 20 weeks of age, female mice carrying one extra copy of Fto weighed 11% more than their normal littermates, and those carrying two extra copies of Fto weighed 22% more than their littermates. Both normal and genetically engineered mice put on weight if fed a high fat diet, but the effect was greater in mice carrying extra copies of Fto. For example, after 20 weeks, female mice carrying one extra copy of Fto weighed 9% more than their littermates, and those carrying two extra copies of Fto weighed 18% more than their littermates.

Mice carrying extra copies of Fto showed greater fat mass than normal mice. At 20 weeks of age, compared to their normal littermates, female mice carrying one extra copy of Fto had 42% higher fat mass, and those carrying two extra copies had 85% higher fat mass. Similar results were found for male mice.

Mice carrying extra copies of Fto ate more than the normal mice, when fed either a normal diet or a high fat diet. There was no difference in the level of activity of the normal mice and the mice carrying extra copies of Fto.

How did the researchers interpret the results?

The researchers conclude that over activity of the Fto gene leads to obesity in mice fed either a standard or a high fat diet, mainly due to increased food intake. They suggest the variants of this gene that have been linked to obesity in humans may have a similar effect, and that this mechanism could potentially be targeted by anti-obesity drugs.

Conclusion

This research has provided an insight into the effects of Fto gene activity, food intake and obesity in mice. The fact that variations in this gene have also been linked to human obesity suggests the results may also apply to humans.

It is important to note that the single letter variations linked to obesity in humans may not have as great an effect on weight as carrying extra copies of the gene. To illustrate this fact, humans carrying two copies of the ‘at risk’ form of a variant in this gene only weigh on average about 3.4% more than people who do not, as opposed to the genetically engineered mice in this study which weighed up to 22% more than normal mice.

Future studies could look specifically at the whether the variations linked to obesity in humans do in fact increase activity of the Fto gene and have similar effects on appetite and weight to those seen in mice.

Although the results suggest that over activity of the Fto gene may influence appetite in humans, much more research would be needed to identify compounds that could potentially target this gene’s effects to reduce the risk of obesity. These compounds would then need to be thoroughly tested in animals before reaching human testing, and then undergo thorough human testing before they could be marketed for human use. This process takes a long time and many compounds fail to complete this process, either because they are not effective or because they are not safe.

Obesity is a serious problem and studies such as these help scientists to understand what genetic factors might influence whether a person becomes obese or not. However, this study does not suggest that people carrying the ‘at risk’ genetic variations in Fto cannot maintain a healthy weight or that they cannot lose weight by reducing food intake or increasing physical activity.


NHS Attribution