A fat gene which makes an adult six times more likely to be obese has been found by scientists.
Around 1 in 6,500 adults, or around 10,000 people in the UK, are thought to have the faulty version of the BSM gene, also known as “Bassoon”.
It is active only in the brain and scientists believe it is the first fat-linked gene so far discovered to be exclusively associated with adulthood obesity and not lifelong obesity, including in childhood.
It is also more potent than any other genes previously found to increase the risk of obesity.
How the gene causes obesity is unknown but the scientists think it may be that affected people have issues making new neurons and the subsequent neurodegeneration could worsen appetite control.
Around 70 people in a study of the half a million UK Biobank participants were found to have the defective gene. Analysis shows these people had a six-fold increased risk of being obese as adults.
A second gene, called ABPA1, is also found in the brain of people and increases the risk in adulthood two-fold, the study found, but less is known about this particular gene.
Big mutations
“These are whacking great big mutations that were not anything subtle,” study author Prof Giles Yeo, from the MRC Metabolic Diseases Unit, told The Telegraph.
“Previously discovered genes have almost always been associated with childhood obesity. Big children, big adults, essentially.”
He said that this is the first gene linked solely to adult obesity and those who possess it are up to 10kg heavier, on average, which equates to an extra four BMI points.
“It is reasonably rare, we are not saying it is a common cause of obesity, but it is present in the general population and it does really have a big difference in body size,” Prof Yeo added.
The work could be used to screen people with excessive weight for the gene but targeting it directly as a treatment is unlikely to work as it is ubiquitous in the brain. Bassoon plays a key role in how signals are transferred around the brain, passing them across the gaps between neurons.
The faulty gene, the scientists think, may slow down the creation of new neurons and this may interfere with the brain’s ability to rein in hunger and appetite.
“We think what is happening – and this is just thinking at the moment because we haven’t really nailed it down – is that having these mutations may very well slow down the ability to generate a couple of new neurons every so often,” Prof Yeo said.
“The hypothesis is that mutations in this gene influence the circuitry controlling food intake as we get older and as we get into adulthood.”
Faulty genes
The faulty genes, the scientists think, may be interfering with the sensation of satiety so that even though the body is full, the mind wants more.
Drugs which are known to help weight loss, such as Ozempic and Wegovy, work by interfering with the brain’s processing of satiety and therefore stop the sensation of needing to eat.
However, this category of drugs, known as GLP-1s, work by interfering with a different pathway in the brain, and will likely have no impact on the hunger caused by the flawed Bassoon gene.
Prof Yeo added: “Bassoon probably does slow down the effectiveness of how these drugs will work, I think. We don’t know yet, just to be clear, but the drugs will probably still work and you’ll still lose weight on them. I predict that weight-loss drugs will work in people with this gene, but not as well.”
The true mystery the scientists are now trying to crack is why this gene, which is present from birth, only takes effect in adulthood.
Future studies on animals will induce the genetic condition as it is too uncommon to easily study in people and see what, and when, the gene becomes active.
It is possible, the scientists say, that it is linked to increased autonomy in adulthood or is a hormone-induced phenomenon brought on by puberty.
The findings are published in Nature Genetics.
