A FAULTY circuit in the brain can trigger binge-eating and lead to severe obesity. The malfunction is caused by mutations in one of the proteins that relays the 鈥淚鈥檓 full鈥� message to the brain.
The mutations appear to be the most common genetic cause of overeating yet discovered. If a treatment can be developed, it could make it easier for people with the mutations to lose weight and help prevent them from becoming obese in the first place.
The gene in question codes for the melanocortin 4 receptor found in the brain鈥檚 hypothalamus. MC4R picks up signals from a protein that is activated by leptin, a hormone that tells us when to stop eating.
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If all is working well, then appetite-suppressing signals are relayed by the receptor to parts of the hypothalamus, the area of the brain that controls appetite. But if the receptor is faulty, it does not respond to the signal and people just keep on eating.
A team led by Stephen O鈥橰ahilly at the Cambridge Institute for Medical Research in Britain found that of 500 people who became obese early in life, 6 per cent had an MC4R mutation (New England Journal of Medicine, vol 348, p 1085).
Children whose MC4R receptors didn鈥檛 function at all chose to eat three times as much breakfast as people without the mutation. Children with partially functioning receptors ate an intermediate amount.
Just looking at the state of the receptor allows you to predict with reasonable accuracy how much someone will eat for breakfast, O鈥橰ahilly says. When it comes to linking genetics with behaviour, he adds, there are few examples that are as good as this.
The team鈥檚 findings are backed up by other research in the same journal suggesting there is a strong link between MC4R mutations and binge eating (vol 348, p 1096). All 24 severely obese people in the study who had a MC4R mutation were binge eaters, while only 14 per cent of 445 other obese patients ate in this way.
The team鈥檚 work raises the possibility of identifying those with genetic variations that make them prone to obesity and giving them specific treatments, rather than the 鈥渙ne-size-fits-all鈥� anti-obesity drug that many companies are racing to develop. But as yet there is no treatment for people with mutations in MC4R.
Where only one of the two copies of the gene is faulty, it might be possible to develop treatments that boost the expression of the normal copy. An alternative approach would be to find ways to bypass the faulty receptor completely.
There are likely to be many similar discoveries. While overeating is of course the main cause of the epidemic of obesity in rich countries, many obese people probably have one or more genetic variations that make them prone to becoming overweight. Most variations like this make little difference when conditions are tough, as in most of our evolutionary past. But when food is plentiful and exercise optional, their effects become apparent.