People with the FTO gene have higher levels of ghrelin, which makes them hungrier, even after eating. Photo / 123RF
Doctors have long insisted it’s weak willpower that makes us overweight – but there is far more to the story.
At the age of 59, I’m happy with my fit body. I’m not skinny, but I’m a healthy size 12. However, all my teenage and adult life, I’ve struggled with my weight putting on pounds quickly. Food has felt like it’s the enemy.
I’ve yo-yoed from a hard-won size 10 to a clinically obese size 16-18 with a BMI of 31. In both my pregnancies – at 38 and 41 – I gained more than 4st (25kg). A few years ago, I visited an Austrian spa renowned for its strict diet, but I couldn’t sleep because of my growling belly.
I’ve always envied seemingly “naturally skinny” women – those who “forget to eat” and never diet. So, when nutritionist Kim Pearson introduced a new genetic test to her clinic, enabling clients to understand their issues, for personalised weight-loss plans, I was keen to try. (There are other tests available, though not all are as comprehensive.)
The Intelligent Weight Loss DNA Test looks at more than 40 genes and 50 SNPs (single-nucleotide polymorphisms, or variations in DNA), known to affect hunger, appetite and metabolism. It involved a simple cheek swab, done at home, posted to a lab.
After receiving my results, two weeks later, there followed a Zoom consultation with Pearson. “I could tell at a glance you are someone who has likely struggled with their weight,” says Pearson. This may sound depressing, but I was happy learning there were reasons for my weight, aside from moral failure.
She explains that our appetite is primarily regulated by two hormones: ghrelin, which makes us hungry, and leptin, which makes us feel full and stop eating. “Genes that influence the function of these hormones make a big difference to our eating behaviour and weight control,” she says.
“For most of us, no single ‘fat gene’ is responsible for our weight issues. Rather, many different genetic polymorphisms combine to create a unique set of challenges.”
Most strikingly, my test revealed I have a common “risk” variant of one of the first discovered, best understood and most influential obesity genes. “It’s called the FTO gene, which stands for ‘fat mass and obesity’, but it can be referred to as the “fatso gene,” admits Pearson.
Everyone inherits two copies of the FTO gene, one from each parent, and studies show that if you are one of the 16 per cent of people who have inherited two high-risk copies, the lifetime risk of developing obesity increases by at least 50 per cent. If, like me, you are one of almost half the population with one, your risk goes up by 20 to 30 per cent. I suspect mine came from my father, who was obese from midlife, developed Type 2 diabetes and suffered heart attacks.
It turns out that us fatsos have higher levels of ghrelin, which makes us hungrier, even after eating. Scans also reveal that fatsos respond more enthusiastically to pictures of high-calorie food in an area of the brain linked to the control of eating, cravings and reward.
Moreover, an Oxford University study discovered that people with the mutated FTO gene seemed to make more fat cells when they overeat, compared to people without it. This additional storage space encourages the body to hoard fat, rather than burn it.
Finally, having a risk copy of my variant – gloriously named “rs9939609″ – increases the risk of Type 2 diabetes. Women with my risk gene may be twice as likely to gain “excessive” amounts of weight during pregnancy than those without it.
The test also looks at the POMC gene, also known as the “hungry labrador” gene. Labrador dogs lack any POMC gene, hence their insatiable appetites. My POMC gene is shorter than average, which means, says Pearson, that it likely makes fewer appetite-suppressing hormones.
Other gene variants flagged in my report are associated with less sensitivity to leptin, a propensity to fat storage when eating starchy carbs and fat, and a higher risk of insulin resistance.
As a health writer, I found the science of all this fascinating, and as a woman, I found it almost reassuring to know I wasn’t just randomly greedy, but fighting my biology.
Luckily, I do not have a mutated MC4R gene. One in 330 people carry at least one copy of this gene, and by the time they turn 18 years of age, they’ll be an average of 18kg heavier than someone without the mutation.
The truth is, thanks to our unique genetic make-up, many of us will find it harder to control our weight. The dice is loaded against them from birth. A very unlucky few have single genes that cause a catastrophic loss of leptin, the “fullness hormone”, and are often obese from early childhood.
Decoding the genetics of obesity is key to finding treatments. Appetite-reducing drugs such as Ozempic could be particularly useful for people whose genetics make them hungrier than others.
But the big question remains. If weight is so strongly influenced by genes, which are relatively stable, why has obesity only boomed in recent years?
For example, until the 1940s, people in the US with mutated FTO genes weighed pretty much the same as everyone else. Yet, according to NHS figures, from 1993 to 2021 alone, the proportion of overweight or obese adults in England rose from 52.9 per cent to 64.3 per cent.
Giles Yeo is one of the foremost experts in the genetics of weight. A professor at the University of Cambridge, his research focuses on how the brain controls food intake and the role of genetics in eating behaviour.
“Forty and 70 per cent of the variation of our body weight is down to genes,” he says. “But the flipside of this is that between 30 and 60 per cent is going to be down to the environment, because obesity results from interaction between environmental and biological factors.”
While we can’t change our genes, their activity can be dialled up or down by other factors. Some studies have shown that eating a high-fat diet, leads to a higher BMI in people with FTO risk genes such as mine.
The good news, according to Yeo, is that the FTO gene is particularly responsive to exercise. “Getting more active can reduce the risk of obesity associated with your risk gene by a third,” he says. We all know the “eat less and move more” mantra – but the same is not true of other obesity-related genes.
The exercise impact on FTO could explain why I’m slimmer as a gym-going 59-year-old than when I was in my 40s, and too exhausted working and raising small children to spend time exercising.
No doubt, the FTO gene would have helped my ancestors tuck away extra pounds to survive famines, but nowadays food is readily available and our jobs are often sedentary. Plus, there are always those Netflix nights.
Since learning my results in May, I’ve tweaked my diet (measuring olive oil, rather than splashing it on my food), eating more protein, and working harder at the gym, including weight training. As a result, I’m confident in keeping my weight controlled. As Pearson notes: “Your genetics are not your destiny.”