Can Our Genes Make Us Fat? (FTO)

Heritability studies have found that genetic differences may account for between 40% to 70% of how susceptible a person is to becoming obese [R, R, R]. This means that while diet and lifestyle certainly play a big role in how much we weigh, so too can our genetic make-up!

How much a person weighs depends on a large number of different metabolic processes and pathways, including everything from appetite control to energy expenditure. In this light, it’s not surprising that there are many different genes that have been associated with weight — over 100 have been identified so far [R]!

However, it turns out that some genes can have a larger impact than others. In this post we’ll be focusing on FTO — appropriately named the fat mass and obesity-associated gene — which is one of the best-studied genes when it comes to body weight and obesity.

If you believe that your genes are making it more difficult to lose weight, talk to your doctor about the information in this post before making any significant changes to your lifestyle or diet.

The FTO gene was the first gene to be linked to obesity. This link was initially discovered in Europeans, but studies have since confirmed the association in populations across the globe. According to many scientists, FTO continues to be the gene with the largest known effect on body weight to this day [R, R, R, R, R].

A SNP in this gene, rs9939609, has been particularly well-studied across all ages and in many different populations. According to hundreds of studies and at least 6 different meta-analyses, the minor ‘A’ allele of this SNP is associated with increased weight gain and higher rates of obesity [R, R, R, R, R, R].

However, despite this strong body of evidence, there are also a few studies that failed to find an association between this SNP and body weight, while others have reported that these associations may depend on additional factors such as gender or gene activity (methylation) [R, R, R]. In other words, it’s likely that when it comes to this gene, it’s also the context the gene is found in that matters. Hopefully, future studies will provide more detail about exactly how, when, and why this gene affects body weight.

The FTO gene was the first gene to be linked to obesity. Studies suggest that the ‘A’ variant of the rs9939609 SNP is associated with increased body weight and higher rates of obesity.

There is a lot that is still unclear about FTO, but studies suggest that this gene works as a sort of “master switch” that controls a variety of other weight-associated genes and pathways in our bodies [R, R].

One of the major ways that FTO may affect body weight is through its influence on appetite. For example, the FTO gene is highly active in the hypothalamus, a region of the brain that is responsible for controlling appetite [R, R].

Animal studies show that when FTO is artificially overactivated in mice, they tend to eat more and become overweight [R].

Relatedly, scientists have found that the ‘A’ allele of the rs9939609 SNP makes the FTO gene more active (increases its expression), which further speaks to the potential link between appetite control and weight gain [R].

Studies suggest that FTO may work as a “master switch” that controls other weight-associated genes and pathways — especially in the regions of the brain associated with appetite.

There has been a lot of research into how exactly the rs9939609 SNP affects our relationship with food. A number of human studies suggest that the ‘A’ allele is associated with:

• Higher levels of ghrelin, also known as the “hunger hormone” [R]
• Greater food (and total energy) intake [R, R, R, R]
• Increased preference for higher-calorie foods [R, R, R, R, R]
• Increased enjoyment of food [R]
• Feeling less full after meals [R, R, R, R]
• Eating in the absence of hunger [R, R]
• Food cravings [R]
• Emotional and binge eating [R]

Additionally, some research even suggests that this SNP may affect our psychological responses to food (or food-related cues)! For example, according to several brain imaging studies, people who carry the ‘A’ allele have a stronger response to food in the reward regions of the brain, as well as a weaker response in brain regions involved in emotion and impulse control. This suggests that people with this allele might have a harder time controlling their eating behavior, which could further account for this SNP’s associations with body weight and obesity [R, R, R].

One especially interesting study even looked at how this gene might affect the way people respond to  advertisements for food. Researchers focused on children, who recently finished eating a meal and were watching a 30-minute TV show. According to these researchers, seeing a food commercial increased the odds that a child would reach for the advertised snack despite already being full. Furthermore, each ‘A’ allele for this SNP increased the amount of snacks kids ate despite previously having a meal of their choice [R]!

So are people with ‘A’ alleles more easily influenced by food ads? It’s an interesting possibility, although additional studies in adults will be needed to give a definite answer.

It’s also important to note that while the studies mentioned above are promising, the exact mechanisms by which FTO (or the rs9939609 SNP) affects weight are still not completely agreed upon yet. Another potential weakness of these studies is that many of them rely on subjective reports from the participants about what and how much they eat, which are not always reliable measurements. Finally, some studies have failed to find a link between food intake and this SNP, while others offer alternative explanations for its mode of action altogether [R, R, R]. In other words, the existing science is suggestive, but isn’t completely settled yet! We will update the post as we learn more.

According to some studies, the ‘A’ allele of rs9939609 may affect the way people respond to food. People with this variant may feel less full after eating, may prefer high-fat and high-calorie foods, and may eat more in general. In addition, some studies even hint that people with the ‘A’ allele may be more likely to eat in response to emotional cues and food ads, making it a bit harder for them to control their overall food intake.

In addition to its potential influence on appetite and hunger control, this FTO SNP may also have metabolic effects that affect how the body actually processes the food we eat. For example, several studies suggest that the ‘A’ allele of rs9939609 may be linked with higher insulin resistance, which is one of the main factors that can cause diabetes [R, R, R, R].

Following on this, a meta-analysis of data from over 40,000 Scandinavians found that people diagnosed with type-2 diabetes were more likely to carry the ‘A’ allele for this SNP. This study’s authors also concluded that having the ‘A’ allele may make a person more likely to develop type-2 diabetes over time [R].

However, in another meta-analysis of over 150,000 people, this SNP’s association with diabetes was found in some populations, but not others [R].

Because the studies are not unanimous, it’s still too early to draw a final conclusion about the exact role of this SNP in overall metabolic health.

Some studies suggest the rs9939609 ‘A’ allele may be associated with insulin resistance and type-2 diabetes.

As previously mentioned, the ‘A’ allele of the rs9939609 SNP increases activity of the FTO gene. This, in turn, is associated with increased weight gain, obesity, and possibly metabolic disturbances such as insulin resistance.

You can see your genotype for this SNP in the table below:

About 40% of people have the ‘AT’ and 14% the ‘AA’ genotype.

The ‘T’ allele is linked to normal body weight, more satiety after meals, and possibly healthier dietary choices [R, R, R].

In contrast, according to some studies, people carrying the ‘A’ allele may [R, R, R]:

• feel less full after eating
• prefer energy-dense foods
• eat more in general
• be more likely to eat in response to emotional cues

Note that this doesn’t mean that everyone with this variant will be overweight or obese! It just means that in a large population, people who have this variant tend to weigh more on average, and are more likely to be obese.