Genetic changes in a brain receptor for serotonin cause obesity and social anxiety.
In a study published in the journal Nature Medicine, we have shown that genetic changes in a gene called the serotonin 2c receptor can cause obesity. Serotonin is a chemical in the brain which affects mood. Medicines which increase the amount of serotonin in the brain are commonly used to treat depression and anxiety. These medications work through a range of different serotonin receptors so while they are often very effective at treating depression and anxiety, they often have side effects including weight gain. Understanding exactly how serotonin works in the brain could lead to the development of new more targeted medicines for these conditions.
By studying over 2,000 people in the GOOS cohort who gained weight from childhood, the Cambridge team found 19 people who carried genetic changes in one particular receptor, called the serotonin 2c receptor. When the team studied the function of these genetic changes in the lab, they showed that the receptor was not working properly, suggesting that these faulty receptors are the cause of severe obesity in some people.
“This study drives home the fact that genetics plays a major role in why some people have a bigger appetite and develop obesity,” says Professor Farooqi of the University of Cambridge.
In work led by their close collaborator, Professor Yong Xu at Baylor College of Medicine, Houston, USA the team found that mice who carried the same change in the serotonin 2c receptor also developed obesity. They could show that a faulty serotonin 2c receptor affects the function of a key pathway in the brain called the melanocortin pathway. As medicines that improve the function of this pathway already exist, this finding could pave the way for treatment of people with obesity due to this genetic condition.
The team had noticed that some people with a faulty serotonin 2c receptor also had social anxiety. When they tested mice with the faulty gene, they found the mice were also really anxious and less likely to socialise with other mice.
Anxiety is a common feature in people living with obesity. This association may reflect the widespread stigma and discrimination people with obesity face and/or childhood experiences which influence the risk of both obesity and anxiety. However, in some people a faulty serotonin system may directly contribute to both their obesity and their social anxiety.
This study provides valuable information that can be used to develop new treatments to help people with both obesity and anxiety.
