Gene variant that turns off fullness signal makes people gain weight

Obesity may be caused by a mutation in our genes and not just our environment.

A study has shown that a mutation in the melanocortin 4 receptor (MC4R) gene could contribute to obesity. The activation of the gene helps to stop people from eating when they are full; a mutation in the gene means a lack of this signal, which leads to over-eating and weight gain.

'MC4R is the volume dial. If it's not working even partially people gain weight; if it's not working completely people gain a lot of weight,' Professor Sadaf Farooqi from the University of Cambridge and co-author of the paper told the Telegraph.

The paper, published in Nature Medicine, takes data and DNA samples from the Children of the 90s study hosted by the University of Bristol. With almost 6000 participants and 80 percent of the mothers being pregnant when recruited between 1990 and 1991, the researchers analysed the DNA samples to see how common the mutation was and how those with it had grown. 

Having the mutation does have a substantial impact on BMI, weight, and fat mass, with some of these effects seen from the age of five. By 18, those with the mutation were, on average, 18kg heavier than those without the mutation.

'Our findings show that weight gain in childhood due to a single gene disorder is not uncommon. This should encourage a more compassionate and rational approach to overweight children and their families.' added Professor Sir Stephen O'Rahilly, joint corresponding author from the University of Cambridge.

Based on the data, researchers suggest that 1 in 337 people in the UK could carry the mutation, double than what had been previously reported. To help reduce obesity, those with the mutation identified by genetic analysis would need to take measures early in life through exercise and diet, or therapeutic approaches.

Environment is also a key factor in obesity. 'These genes and genetic mutations are there and have been there. The change is in our environment. It's our environment that has driven this,' co-author, Dr Giles Yeo, also at the University of Cambridge, told the Telegraph.

In future, it is hoped that understanding the brain pathways controlled by MC4R could contribute to the development of therapies that bypass the failed signal, helping people to maintain a healthy weight.