Obesity can begin in the brain, gene study shows

Hope for new treatments for the 400 million people WHO believes are too fat

Eating too much and putting on weight may be more to do with one's state of mind rather than a metabolic imbalance, according to a study that reveals six genes linked with obesity.

Five of the genes are active in the brain which is why scientists believe that the discovery could lead to new obesity treatments aimed at changing people's psychology towards food rather than their physical desire to eat.

The study was based on a genetic analysis of 90,000 people, whose DNA was analysed for the smallest mutations, and compared against their body mass index, the scientific assessment based on their height and weight. Scientists found six genetic variants that appear to cause a small but significant increase in weight. If someone carried all six variants they would typically be between 1.5kg and 2kg (3.3lb and 3.4lb) heavier than the average person.

That five of the variants are close to genes active in the brain raises the prospect that being overweight is due to the way the brain is wired from birth. "It might seem remarkable that it is the brain that is most commonly influenced by genetic variation in obesity, rather than fat tissue or digestive processes," said Ines Barroso, of the Wellcome Trust Sanger Institute, near Cambridge.

"Until 2007, no genetic associations had been found for common obesity, but today almost all those we have uncovered are likely to influence brain function," said Dr Barroso, whose study is in the journal Nature Genetics.

It is estimated that between 40 and 70 per cent of the variation in body mass index is caused by genes rather than environment but until recently the only genes that have been linked with obesity are those that cause changes to the body's physiology, such as the LEP gene responsible for the leptin hormone, which controls energy intake and expenditure.

The latest study has begun to shine the spotlight on the many other genes that each play a small but significant role in determining the common obesity seen in the general population, which is exacerbated by high-calorie foods and lack of exercise.

Ruth Loos, of the Medical Research Council Epidemiology Unit, said: "Very occasionally, mutations in genes active in the hypothalamus have dramatic consequences for weight gain, such that people carrying these mutations are severely obese. Such mutations might be considered exceptional. We suggest that the picture for common obesity is very similar. Many or most genes associated with increased body mass index are active in the brain."

The scientists, part of a large consortium from the UK, America and Iceland, believe they are only just beginning to discover the many dozens of genes implicated in raising someone's risk of becoming obese.

The World Health Organisation estimates that 400 million people are clinically obese, in developed and develop-ing countries, and many of these are at high risk of type-2 diabetes. Professor Mark McCarthy, a diabetes researcher at Oxford University, said the findings could lead to new treatments for other conditions with a genetic basis.