Bouchard found that our genes influence our resting metabolism, fat mass, percent of fat and abdominal visceral fat, and cholesterol levels. He and his colleague Angelo Tremblay discovered one important exception, though — a vital piece of information for those seeking to control their weight. They found that when subjects performed vigorous exercise, genetics didn’t matter as much. Bouchard’s definition of “vigorous” was any exercise that caused metabolism to increase by six times or more over resting metabolism (which can be achieved by running about 4 to 6 mph or cycling about 12 to 16 mph, or doing other activities that produce rapid breathing and sweat within a few minutes).
The lesson is clear: Once we enter a specific range of strenuous exercise, the body kicks in to lose fat, no matter what our genes want.
New technological advances are allowing for more specific investigation of our genes. For example, individuals with variations in a gene called FTO tend to desire high-calorie foods more often and have more fat as a result. This genetic variation causes an almost twofold increased risk of obesity compared with those who don’t inherit it.
Colin Palmer at the University of Dundee in Scotland conducted one study that shows the effects of the FTO gene. He assessed almost 100 schoolchildren to see whether they carried the FTO variant gene or the normal gene. He then evaluated what the children ate by allowing them to take food from a buffet that included an assortment of fruits and vegetables, as well as higher-calorie foods such as chips and chocolate. When he analyzed what they consumed, he noticed that children with the FTO gene variant had eaten more of the higher-calorie, energy-dense foods compared with children with the normal gene.
“They had the same amount of food, the same mass of food, it was just the higher-calorie foods,” Palmer says. Not surprisingly, children with the variant gene also had about 4 pounds more body fat. The FTO gene is thought to be expressed not only in the brain, where it increases our desire to eat fattening foods, but also in fat tissue.
Harvard Medical School researcher Melina Claussnitzer and her team found that a single variation in the FTO gene caused fat cells that would normally become healthier beige to turn into white fat cells instead. Beige fat cells have the potential to turn into energy-burning brown fat cells when activated by exercise. But in people with the FTO mutation, fewer cells become beige and more turn into energy-storing white cells. So the result of the FTO mutations is a drive to eat higher-calorie foods paired with less calorie burning and more calorie hoarding — a challenging combination for any dieter.
Although individuals with variants in their FTO gene have almost double the risk of obesity compared with those who do not inherit the gene, “having the FTO variant doesn’t mean one is destined to be fat. We can still control what goes in our mouths, though it may be more work for some than others,” Palmer explains.
Not all fat caused by genetics is a bad thing — and some of it may actually be protective. Ruth Loos is the director of the Genetics of Obesity and Related Metabolic Traits program at Mount Sinai Hospital in New York. She’s slender, with short, wispy blond hair that frames her angular features.
Working with Bouchard, Loos grew fascinated with the genetics of fat and metabolism, and eventually went on to establish her own lab at Mount Sinai. As she set out to design her research, she noticed that many genes being identified were linked to high BMI, which simply compares someone’s weight with their height. Loos realized BMI isn’t the best measure of fatness because it doesn’t separate fat mass from lean tissue like muscle.
In other words, if you’re a bodybuilder with only 7 percent fat but a lot of muscle, your BMI will be high, perhaps the same as that of someone who is obese with lower muscle mass.
The good news is, unless you have one of the very rare genetic mutations that undeniably cause obesity, your genes are just one factor in your weight profile.
Loos wanted to tease out which sections of DNA had to do with fatness, not just weight. So her team conducted an analysis of the genetic data from 36,626 individuals to see which genes were associated with body fat. From this research, Loos found that fatness was significantly linked to variations in the FTO gene and a gene called IRS1. It was already understood that FTO variations were associated with being overweight, encouraging kids to seek fattier foods, for example. But the linkage of the IRS1 gene to fat was new.
As the team analyzed the data, they uncovered a mystery. One variation of the IRS1 gene caused lower fat in men. At first, this seemed like a lucky gene to have. But as Loos analyzed the data further, she saw that while men with this variant indeed had less fat in their arms, legs and trunk, they also had higher triglycerides — fat found in the blood — and lower good cholesterol in their blood and increased insulin resistance, all signs of ill health.
How could this be? They were thinner than men without the variant, and thinness should lead to better health, not worse. More puzzling, this variant didn’t seem to affect women in the same way.
Loos and her team looked further. Perhaps this adverse metabolic profile was linked to how fat was distributed. Her team reviewed measurements for subcutaneous fat, the healthier fat which sits under the skin, and visceral fat, the unhealthy fat that surrounds the organs. They found that men with one IRS1 variant (let’s call it variant A) had lower subcutaneous fat and more visceral fat compared with those without the variation.
However, the men with variant B were fatter but also healthier. Why would the gene that produces more fat protect you against disease, Loos wondered. Slowly, she and her team pieced together an answer. IRS1 contains the code for a protein that’s involved in mediating cells’ sensitivity to insulin, a hormone that helps the body use sugar and store fats. She found that IRS1 variant A was associated with lower expression of this protein in subcutaneous fat and visceral fat. So, cells in these areas weren’t as sensitive to insulin and weren’t internalizing glucose and fats. This occurred in men much more than in women.
In addition, IRS1 variant A was inhibiting the expansion of fat tissue. With no place to go, more fat was hanging around in the blood, causing health issues. On the other hand, those with IRS1 variant B were able to easily expand their fat tissue. So they were a little chubbier because the fats in the blood went where they belonged — into fat.
Loos’ findings described a new kind of fat gene. Other gene variants — like mutations in FTO or the gene for leptin, an energy-balancing hormone — had been linked to overeating or fat cell type. But IRS1 was the first that was linked specifically to fat cell creation. When we don’t create new fat cells to house our circulating fats, we’re prone to more diseases. With less fat, we may appear to be healthier, but may actually be in danger of developing diabetes and other diseases.
“Genes that increase your risk of obesity can also protect you from Type 2 diabetes [and] cardiovascular disease and give you an optimal lipid profile,” Loos says. “These are what we call the healthy obesity genes. So these individuals who had the variant to increase fatness actually were good fat storers. They store the fat where it should be stored. And it protects their liver, it protects their muscle, it protects against visceral fat. And that fat protects them against disease as well. So these [good] genes, they do exist.”
You can undergo a diagnostic test to find out whether you have any known gene variants that are associated with obesity. If you have such a variant, are you doomed to a life of flabbiness? The good news is, unless you have one of the very rare genetic mutations that undeniably cause obesity, your genes are just one factor in your weight profile.
In the end, daily actions matter more. How much we decide to eat, what we eat and how much we choose to exercise will, in the majority of cases, trump our genes. Fat genes like the FTO variant, however, make it harder to stay on track and keep weight down.
“You may be genetically susceptible to become obese, but it doesn’t mean that you’re destined to become obese,” Loos says. “Genes load the gun, and environment pulls the trigger.”