Are your genes making you fat?

Your DNA determines everything from your height to the colour of your eyes, but can you also be genetically predisposed to being fat? We asked geneticist Dr Sam Decombel if that’s the case and, if so, is there’s anything you can do about it

Do you struggle to shed body fat? Do you find it seemingly impossible to lose those last few final pounds? We often think that diet and lifestyle are the main causes of weight gain, and these two factors have an undeniable impact. But can you also inherit a predisposition towards being fat? If your parents are overweight are you destined to be overweight too? Can you really blame your genes, which are short sections of DNA, for your inability to cut down to size?

The first evidence that genetics might play a role in how easily we gain weight came from studies on twin in the 1980s. In this type of research, academics look at the differences between identical and non-identical twins to determine how much of a characteristic is genetic, and how much is because of a shared environment.

Identical twins share both a genetic code and home environment, so comparing them to non-identical twins – who do not share the same genetic code but do share the same environment – provides an estimate of how much of a contribution the genetic element has. In short, they are trying to find the impact of nature versus nurture.

The researchers found that identical twins are much more likely to share a similar waistline than non-identical twins, suggesting that genetics does indeed play a significant role in how predisposed we are to carrying excess body fat.

Gene discovery

However, we had to wait more than 20 years from these preliminary findings for the first concrete evidence of a link between genetics and weight gain.

It came in 2007, when a team of British researchers announced that they had identified a number of genetic variants within a gene called FTO, which stands for fat mass and obesity-associated protein. On average, people with one particular set of these variants weighed 1.6kg more than people with none, and those with two sets – which one in six Europeans have – weighed 3kg more.

So what was going on? What was making those carrying the FTO risk variants gain the extra weight? Was it a slower metabolism, or less efficient fat burning?

Interestingly enough, the answer turned out to be much simpler than that: they ate more food. But more than that, these individuals tended to reach for higher fat foods more often than the non-risk carriers. In short, carriers are genetically programmed to eat more food.

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Energy expenditure

So do FTO risk gene carriers have less willpower than those without? Perhaps, but with good reason. FTO is highly expressed in the hypothalamus, a region in the brain involved in regulation of food uptake and energy expenditure.

While the effect these FTO gene variants are having does not appear to be metabolic in nature – meaning that the effect of food consumed is likely to be no different between risk and non-risk carriers – they do seem to have a role in appetite regulation. This occurs specifically through changes in the levels of certain hormones that act as chemical messengers that tell us how hungry we are, or full we feel.

From a biological point of view, a feeling of hunger occur because of the fluctuating levels of hormones, one of which includes ghrelin, informally known as the ‘hunger hormone’, because of its role in stimulating appetite. Research has suggested that ghrelin levels play a large role in determining how quickly hunger returns after we eat. The faster your ghrelin levels rise after a meal, the sooner you feel hungry again.

Hunger suppression

While the precise mechanism is still to be determined, we know that ghrelin levels in FTO gene risk carriers are not suppressed as strongly following a meal as those with the non-risk version.

What this means is that if you carry the FTO risk variant it’s very likely you will not feel full up when eating, or immediately after a meal, and so consume more food than non-carriers. In short, your genes are instructing you to eat more more food, even though you don’t need it.

There is a good biological explanation for why this variant evolved and exists. Genes that make us desire food and eat as much as possible are an advantage in environments with sporadic or very limited access to sufficient nutrients. As a species we lived in a ‘feast or famine’ environment for the overwhelming majority of our existence, and so a gene variant that allowed some to eat as much as possible when it was available is a huge evolutionary advantage.

But now, for the first time in our history when many of us live in an environment where there is an excess of food available around the clock, this genetic trait has become a huge disadvantage, and it takes a big effort for carriers to overcome this very primeval instinct to eat.

No excuses

Is carrying a copy or two of the FTO risk variant an excuse for being fat? A BBC survey of more than 10,000 people suggested that 70% of us don’t think genes are to blame for obesity, and I would tend to agree with them.

Firstly, this is only one gene among more than 75 found so far that are linked to weight gain, and at my company FitnessGenes I’ve see plenty of people who carry two copies of the FTO risk gene yet manage to control their body fat levels extremely well.

What are these guys doing differently to everyone else then? Obviously you can’t change your genes, but that doesn’t mean that you need to be completed controlled by them if you’re prepared to put in a bit of time and effort. This probably won’t come as a surprise but, according to the research, if you carry the FTO risk variants then the first thing you can do to aid weight loss is get more exercise.

A recent meta-study of more than 235,000 people indicated that physical activity is a significant modifier of FTO, and FTO risk carriers with an active lifestyle can reduce their odds of obesity by 27%.

It’s believed that part of this impact is because of the effect that exercise has on appetite. Working out is known to alter levels of the ‘hunger hormones’, including ghrelin, and a growing body of evidence indicates that a short and intense bout of exercise is the most effective for suppressing appetite and the effects can last for between two to ten hours.

Avoid high-fat foods
From a nutritional perspective carriers might way to try to avoid high-fat foods in a bid to better control their hunger hormones and rein in appetite.

A study examining the effect the FTO risk variant had on muscle mass and body-fat levels in response to different diets found that carriers were significantly less likely to complete a 10-week calorie-restricted high-fat, low-carb diet than those on a low-fat, high-carb diet, possibly because they were less responsive to the filling effects of fat.

The type of dietary fat consumed also seems to matter: those FTO risk carriers consuming more than 12.6% of their total daily energy intake from saturated fat – such as found in meat and dairy products – further increased their obesity risk.

So, if you think you might be have the fat-storing variant, what can you eat? High-protein diets are known to fuel weight loss because protein makes you feel fuller for longer than carbs or fats.

It’s possible that certain amino acids that make up protein contribute more to that full feeling we get after a high-protein meal. The amino acid L-cysteine, found in protein-rich foods such as meat, poultry and eggs, in particular appears to be associated with regulation of food intake, with recent research showing that the greater the consumption the greater the reduction in hunger and ghrelin levels in humans. This doesn’t mean you should supplement heavily with L-cysteine, however, because at least one study has linked very high dosages to oxidative stress, which is the imbalance between the production of free radicals in your body and its ability to counteract their damaging effects through neutralisation by antioxidants.

Watch what you eat
If you are worried that you are predisposed to eating more food and carrying more body fat, then the key is to get more exercise, with a focus on high-intensity interval-style training, and avoid overconsumption at mealtimes by paying more attention to what you are eating. And try to cut back on snacking: it’s very easy to mindlessly eat because of routine or boredom when we’re not actually hungry, or eat too much of the wrong types of food.

Developing good eating habits, like preparing your meals for the week in advance, and eating more slowly and consciously, are very simple and effective ways to reduce your risk of piling on the pounds. Your genes may be inherited, but good habits can be learned.

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