A little over a year ago, British researchers discovered a gene that contributes to obesity. This so-called "fat gene," FTO, is closely correlated with body mass index (BMI), and is found in nearly half of people of European descent. The effects of FTO depend in part on how many copies of it a person inherits. People with one copy of the gene are on average 2.6 pounds heavier than people without the gene, in comparison to 6.6 pounds for people with two copies of the gene. Those with two copies of the gene are 67 percent more likely to be obese than those without the gene.
But how does FTO act on obesity, given that human genetics have not substantially changed over the centuries? Why are we getting so fat now? In the never-ending question of nature versus nurture, researchers have long been interested in the role of such genes in the modern obesity epidemic. What is the role of lifestyle relative to genes like FTO? In short, how much will you need to do to fight off FTO's effects? A study conducted at the University of Maryland School of Health and released this week in the Archives of Internal Medicine indicates that, if you really want to fight the fat gene, you're going to have live like a pre-modern European—or the present-day Amish.
The University of Maryland study attempted to examine the role of exercise on FTO apart from the modern diet. And for this, there was an ideal subject group. The study was conducted in Lancaster, Pennsylvania among the state's substantial Old Order Amish community. Old Order Amish are the most traditional of the various Amish sects, all of which originated in Switzerland at the end of the 17th century, and then migrated to the United States in the 18th century. The Amish reject almost all of the conveniences of modern life, including most electricity and the automobile; they try to maintain the lifestyle their ancestors had in Europe, and to keep a separation from the outside world. All of these factors made the Amish ideal candidates for a study of FTO. Because they are all of European descent, FTO is highly prevalent in their community. And, because they eschew most modern conveniences, many Amish are very active, as people were in a pre-modern world. Whether farming or working wood or metal, in the case of the men, or running multi-child households without the aid of modern appliances, in the case of the women, the Amish get a lot of old-fashioned exercise.
To determine the relationship of FTO to physical activity, the Maryland researchers studied 704 Amish men and women. They did detailed genetic testing on these subjects, locating and typing all copies of the FTO gene. They also got objective measurements of the subjects' physical activity by giving them accelerometers, which are worn on the hip and which measure the body's movements. Based on the accelerometer readings, the researchers categorized their subjects as high activity or low activity. "High" amounted to three to four hours per day of moderate activity, such as gardening, housecleaning, or walking (not strolling or running). As Dr. Evadnie Rampersoud, the lead author, who is now at the University of Miami, explains the results, "Having multiple copies of FTO gene variants had no effect on body weight for people who were the most physically active, regardless of whether they were men or women. But in less active people, the association between the gene and increased BMI was significant. This provides evidence that the negative effects of the FTO variants on increasing body weight can be moderated by physical activity." In other words, the gene may predispose you to gain weight—but you can escape that destiny by exercising regularly.
The researchers theorize that genes like FTO have a new dominance in the modern era, as our lifestyles have substantially changed. As Dr. Soren Snitker, the senior author on the article explains, "Some of the genes shown to cause obesity in our modern environment may not have had this effect a few centuries ago when most people's lives were similar to that of present-day Amish farmers." Figuring out how to counter the impact of these genes in the modern era is only just beginning to be understood. "One day," Dr. Snitker says, "we hope to be able to provide a personally optimized prescription to prevent or treat obesity in people based on their individual genetic makeup." But that day is far off; as Dr. Snitker explains: "We are just starting to unravel these complex interactions between genomics and environment. It's really a new age of discovery."