Dr Giles Yeo contributes to the #Co90sDiscoveries series and explains why tackling the global obesity crisis requires genetic understanding, not moral judgements.

Are our genes intrinsically linked to our size? People who struggle with weight gain could be fighting their own biology, which makes them more likely to put on weight. Understanding this will help us tackle obesity with better science, not moral judgements.

Fat genes: Body weight is not a choice 

The World Obesity Federation estimates that more than a billion people around the world will be living with obesity by 2030. This public health challenge is caused by multiple factors – our environment, society and our bodies themselves. The latest research reveals how genes can cause obesity – understanding this relationship is crucial for scientists, policymakers and those of us battling with our weight.

The appetite gene

Obesity often runs in families and as studies over the past 20 years have shown, this can be due to changes in specific genes that significantly alter how each of our bodies handle weight gain.

One of these genes, the Melanocortin 4 Receptor (MC4R), has been linked to early onset obesity since 1998. MC4R produces a protein that sends signals to our brain’s appetite sensors, telling them how much fat we have stored and therefore when we are full. When this gene is faulty, our brains incorrectly deduce that we are lacking in fat stores, triggering our desire to overeat so we gain weight.

Thanks to the detailed health data and biological samples held by the Children of the 90s study, epidemiologists have been able to unravel the role of genes in obesity. These findings shed light on a subject that is more often couched in blame than scientific understanding.

Using biobank data to tackle obesity

Prior to this discovery, little was known about the prevalence and impact of the MC4R gene and how it affected levels of obesity.

Using Children of the 90s data, researchers searched for the MC4R gene in a random sample of 5,724 participants born in Bristol between 1990 and 1991. Whenever a mutation in the MC4R was found, lab tests were conducted to observe the effects.

Researchers found that one in every 337 people (0.3% of participants) may carry a faulty version of the MC4R gene, making their brains sense that they have slightly less fat than they actually do. This drives them to eat more and leads to increased weight gain in childhood. As a result, people with this faulty gene were on average 17kg (or 2.5 stone) heavier by the age of 18. Worryingly, the study revealed that the obesity gene is actually quite common, affecting up to 200,000 people across the UK.

Understanding food intake

“Body weight is not a choice,” says Dr Giles Yeo, a geneticist from the University of Cambridge who has been studying the genetics of obesity and brain control of food intake for more than 20 years.

“For some, it is the cumulative effect of multiple genetic variations, each having a subtle effect. For others, it is a single mutation that has an enormous effect.  Some people, in effect, find it more difficult to say no.”

Weight management strategies

These insights into how the brain’s pathways are controlled by MC4R could help the design of drugs which bypass these signals, allowing people to maintain a healthy weight. They could help to identify people at risk of obesity much earlier in their development.

Dr Yeo, author of the book ‘Why Calories Don’t Count’, says that more evidence like this and scientific understanding is needed to go beyond the flawed approach to weight management that relies on counting calories.

“People living with obesity are not bad, slothful or morally bereft, they are fighting their biology,” he says. “Until we in society, including those responsible for policy, understand this, we will never come up with a cogent and sustainable solution to the obesity problem.”

This research on the MC4R gene is a striking example of how genes affect our weight. There are likely to be further examples that emerge as genetic sequencing becomes more common.