Do these genes make me look fat?
Scientists are probing the complex relationship between our DNA and our diets to unravel the root causes of obesity. But for those seeking a simple solution to the worldwide fat epidemic, their answers may be hard to swallow.
By Madeline Fisher
This paradox plays out strikingly when you compare diabetes risks among people of different cultures or geographic regions. Among the Pima Indians of Arizona, for instance, one-half of all adults have diabetes, one of the highest rates of diabetes in the world. While obesity is epidemic among the Pima community, another factor seems to be at play, says Alan Attie, a biochemistry professor who studies diabetes. Attie points out that while white Americans are considered to be at risk for diabetes when they have a body mass index (BMI) of 30 or above, the figure is much lower for the Pima Indians. A much lower level of obesity puts them at risk for developing the disease.
The same is true of people who live in southern India: Scientists estimate that southern Indians need only hit a BMI of 23 to be in the same danger as a white American with a BMI of 30. So while a six-foot-tall, 175-pound Caucasian male would need to gain about 50 pounds to be considered at high risk for diabetes, a southern Indian man of the same weight and height would already be there.
“So that tells you something about genetics,” says Attie. “There clearly are some genetic factors that are normally silent when you’re lean, but that interact with obesity to bring on diabetes. And they’re much worse in certain groups of people.”
Much like Ntambi and Yen, Attie has been probing this idea in experiments with genetically engineered mice. His lab houses two groups of mice, both of which are morbidly obese. But only one is susceptible to type 2 diabetes. He is now searching for the genes that account for the disparity.
But even as we’re uncovering genetic differences in how we process foods, the foods themselves are growing more homogenous, a trend that could greatly complicate efforts to prevent obesity-related diseases such as diabetes. On the street in Taipei, Taiwan, where Yen grew up, for example, six American fast food outlets have sprung up since he graduated from high school. And Taipei is not alone: As Western staples and processed foods spread around the globe, we’re only beginning to learn what effect those diets will have on populations that have historically not consumed them. Already, obesity rates have been climbing in Asia and other parts of the world, and this has Attie worried about the implications for diabetes. “Although we talk a lot about the diabetes epidemic in the United States and Europe, the diabetes epidemic that is anticipated in Asia is going to be much worse,” he says.
This global transformation is proving significant for Africa, as well. When Ntambi left behind his studies of African sleeping sickness to investigate obesity, he never imagined that someday he’d again be working on an African disease. Sadly, though, that’s exactly what obesity and diabetes have become.
“When I was growing up in Africa, I never saw many obese people. Now I do,” says Ntambi, who travels back every year to Uganda to teach and do research. “So something must be changing, and I think it’s lifestyle and diet.”
Ntambi believes Ugandans, like many Westerners, have grown fatter as they’ve become more affluent, which brings access to more food and time-saving technologies that encourage a sedentary lifestyle.
“It’s a paradox,” he says. “In Africa, when you buy a car or when you have a TV, it’s a sign of prosperity and you would be proud. But if you misuse that technology, it’s going to turn around and affect your health.”
To be sure, recent years have seen a massive investment in research to address this global epidemic. Ntambi’s work with SCD, as well as Yen’s research on MGAT, have pointed two possible routes toward intervention. Based on the knowledge that inhibiting genes such as these change how our bodies store fat and burn energy, several drug companies are now trying to develop a pill that would tilt our metabolic balance away from cherishing fat.
While a weight-loss pill is a tantalizing idea, however, things aren’t quite that simple. For one thing, while mice don’t naturally express MGAT in the liver, people do, and Yen imagines that a drug targeted at MGAT could cause liver side effects not evident from mouse studies. Chemically inhibiting SCD also has potential downsides. Mice lacking the gene suffer from dry eyes and severe skin problems, and their levels of saturated fatty acids rise—with unknown consequences. What’s more, deleting SCD causes the metabolic rates of mice to skyrocket, suggesting that drugs aimed at the gene could possibly affect longevity.
“So, it’s tricky,” says Attie, who has collaborated with Ntambi on several studies of the gene. “But we’ll know. There are a lot of drug companies working on SCD.”
Side effects aside, there is perhaps a bigger reason not to pin all of our hopes on a miracle drug for obesity. Such drugs are bound to be expensive—and therefore out of reach for much of the world’s population, says Ntambi. He has seen it before with diabetes in Uganda.
“Diabetes can be managed by diet, exercise and, of course, by insulin. But insulin is very expensive in developing countries,” he says. “So someone may be diabetic, but not really have access to insulin, or individuals can become diabetic and they don’t know it.”
That’s why, when Ntambi was packing last December for a six-month sabbatical in Uganda, he packed some 3,000 donated kits for monitoring blood glucose levels. During his visit, he handed them out for free so that people could check their blood sugar and get appropriate medical attention. He also hoped, along the way, to educate as many people as possible on ways to prevent obesity and diabetes, since for many Ugandans, changes in lifestyle and diet are likely the best—and possibly only—solutions for good health.
“We’re not saying that you shouldn’t eat a high-carbohydrate or a high-fat diet,” says Ntambi. “You can eat what you like, if you enjoy it, as long as you’re able to have energy balance in the body. The energy coming in has to be counteracted by the energy that is going out.” And in nutrition, that’s as simple as it gets: Expend more energy than you take in, and you’ll shed pounds. We’ve heard it before, but the science of genetics is reinforcing its essential truth by showing us exactly why it works this way. The only question is: Will we listen?
Tags: DNA, Genetics, obesity
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