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Obesity genes reveal why we eat too much

A molecular model of a leptin receptor. The hormone leptin interacts with receptors in the brain to signal when a person is full. © Getty: Laguna Design
A molecular model of a leptin receptor. The hormone leptin interacts with receptors in the brain to signal when a person is full. © Getty: Laguna Design

Scientists are closing in on the genes that make us eat too much, and their findings could lead to powerful new drugs in the future.

Obesity causes over one in ten deaths in some European countries, according to the World Health Organization, as it significantly increases sufferers’ chances of diabetes, heart diseases and hypertension. Unlike other global health threats, its primary cause lies in our lifestyle – modern technology means people exercise less and fatty foods are in abundant supply.

Finding a pill to control appetite is a challenging task. Physiologists are still untangling the mesh of neurons and hormones that regulate our appetite. Now researchers are using genetics to home in on the underlying mechanisms, and it’s leading to powerful new drugs that could help people bring their eating under control.

‘What makes you fat is how much you eat, we don’t dispute that. But genetics is revealing why you eat,’ said Dr Giles Yeo, the principal investigator of EurOCHIP, an EU-funded consortium which has been unravelling the complexities of gut-to-brain communication. ‘This vital information is leading to a spectrum of new treatment possibilities.’

The project works out which genetic anomalies are common to obese people, and then tracks backwards to find out what the impact of these anomalies are on the body.

Get the message

The technique has led them to leptin, a hormone that tells the brain when the stomach is full. Many obese people have developed a resistance to leptin, making it difficult for the message to get through.

‘Genetics is revealing why you eat.’

Dr Giles Yeo, the principal investigator of EurOCHIP

The problem lies in the way leptin pass­­es through the barrier between the bloodstream and the brain. ‘To cross this interface, leptin undergoes a startling series of reactions,’ said Dr Julie Dam at the Institut Cochin in Paris, a partner of the EurOCHIP consortium.

Biochemical imbalances in obese people can result in their bodies releasing too few of the chemicals that allow leptin to pass into the brain. Adding some of these chemicals into the bloodstream artificially could make the message from the stomach clearer, helping people eat less.

Genetics is also being used to highlight why some people are more likely to become obese than others. Projects such as betaJUDO, funded by the EU, used genetic screening to work out that obese children are more likely to have genes that cause the over-secretion of insulin.

Genetic predisposition

‘There is a clear genetic predisposition towards obesity and insulin hypersecretion,’ said Professor Antje Körner, who works with the betaJUDO project as part of her research at the Center for Pediatric Research at Leipzig University in Germany.

She collected DNA from over 2 000 carefully phenotyped obese children to track correlations between individual genes and insulin secretion. ‘Databanks of this kind make it possible to work backwards from the genome and identify the body mechanisms which lead to the disease,’ she said.

The project then isolated insulin-producing cells from the pancreas and exposed them to different environments. They observed that fatty acids enhanced the secretion of insulin, whereas other chemical compounds reduced it.

‘The right dose of these compounds could help regulate insulin production before these children grow obese and develop complications such as Type 2 diabetes,’ said Professor Peter Bergsten at Uppsala University in Sweden, the project coordinator.

The project, now halfway through, will soon test the compounds in animals and plans to begin trials in people within the coming two years.

A healthy diet and exercise remain the best way to tackle obesity, however these new techniques and the pharmaceutical arsenal they could provide will help balance the metabolism of vulnerable individuals, and relieve the close to 200 million obese adults in Europe from expensive, life-threatening medical interventions in the years to come.

Treating obesity with a microchip

Drugs are not the only approach being investigated to tackle obesity.

The European Research Council has given a EUR 7 million grant to Imperial College London’s i2MOVE project, in which Professors Christofer Toumazou and Stephen Bloom have recorded signals of satiety electronically by implanting a microchip in nerve channels connecting the gut to the brain.

By simulating these signals, they hope to inform the body more clearly of when it has eaten enough.

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