Significant to have found gene with link to obesity

Tony Merriman
Tony Merriman
This week a group based at Brown University in Providence, Rhode Island, reported their discovery that a gene called CREBRF is important in obesity in people living in Samoa. University of Otago professors Tony Merriman and Dave Grattan explain why this work is important and how it can contribute to efforts to combat obesity.


Dave Grattan.
Dave Grattan.
The "obesity epidemic'' is an important public health issue.

This is because being obese increases a person's risk factors for suffering from serious diseases such as cardiovascular disease, kidney disease, type 2 diabetes and cancer.

The major sector currently attempting to tackle obesity is public health, largely by encouraging reduced intake of inappropriate energy-dense, nutrient-poor foods. Without any support by governmental policy (e.g. a tax on added sugar), educating people to eat better and exercise more is the current weapon. This approach is yet to have impact and may never work for some people.

Obesity results from an imbalance between calories consumed and calories burned. Therefore, why can obese people just not eat less? The answer lies in our exquisitely balanced inherited biology colliding with our modern environment.

We each eat about 1 million calories per year, and to gain 1kg would take only an excess of energy intake of 6000 calories (0.6%) - 16 calories per day (quarter of an apple).

That we do not gain many kilograms per year is because our brain unconsciously monitors how much food we eat and how many calories we burn, and regulates both our appetite and our energy expenditure to match the two.

And it does this with an accuracy of more than 99% in most of us - meaning we maintain roughly the same weight over many years. Whether you are obese or lean, it is hard to eat less that your brain thinks you need, because you will always be hungry.

So if this biological system is so accurate, why is obesity increasing? Has our biology changed? No - our environment has changed. Food is now readily available. Under these conditions, you might expect that everyone is getting fatter. But this is also not the case.

People who are genetically predisposed to weight gain will gain weight when faced with the present environment. Bad decisions might contribute to this, but the reality is that by far the biggest part of the problem is that the biological response is not able to compensate for the change in the environment.

Better understanding of the biological basis of obesity therefore is an essential ingredient of a multi-pronged approach to tackling obesity. This will allow us to develop better medical and behavioural interventions.

Just like height, we know obesity is heritable. Roughly 60% of the reason why some people get obese and others don't in our current environment is due to genes, with the environment controlling the average weight of the population.

And it is hundreds of genes. Each gene individually plays a minor role but collectively our genetic make-up is very important. We all know someone who seems to eat a lot but stays skinny, or someone who watches what they eat but is a bit overweight and never seems to be able to lose the kilos.

To understand the reasons, geneticists look for differences in the genetic make-up between people who are obese and people who are not. The major genes controlling weight are those that control eating behaviour in the brain. Lean people are genetically lucky, when it comes to body weight.

If we want to solve the obesity problem, we really need to understand the many different biological drivers that lead to obesity - the way our appetite is controlled, the way we absorb food, the way we store fat and the way we regulate energy expenditure.

This is where genetics is so powerful. Our genes are inherited at conception and begin working straight away. So if a gene is associated with obesity then we know that the biological pathway it is in (e.g. hunger control) causes obesity.

This gives us a strong evidence base to design better drugs to help people struggling with obesity, or better, to prevent it from happening. The increased scientific knowledge will allow better medical and behavioural interventions approaches to counter obesity.

The recent genetic study in Samoa is a landmark study that identifies a new gene that increases risk of weight gain. This in itself is a very important scientific finding, but the fact that this gene at the same time protects people from type-2 diabetes shows that the biology linking obesity and type-2 diabetes is more complex than we first thought.

Not only are these results important for Samoan people, they will contribute to understanding in other populations. We hope the ongoing genetic study of Maori and Pacific New Zealanders we are doing with the Maurice Wilkins Centre will fill in gaps in our understanding of the causes of obesity and diabetes in New Zealand.

This information will give us a better handle on how we might develop rationalised strategies to target the different causes of obesity in different individuals in New Zealand.

Current public health approaches focused solely on changing the environment might work in the long-term, or they might not. Our recent history suggests that we need additional tools to help.

In the interim we strongly advocate the importance of biomedical research, including genetic studies such as the Samoan one, to increase our understanding of the biology behind obesity, and to take a more medical approach to this issue. We cannot afford to take a wait-and-see approach.

-Prof Tony Merriman is in the department of biochemistry at the University of Otago and Prof Dave Grattan is in the department of anatomy.

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