Do these genes make me look fat?

It’s hardly a secret that America is fat. Take a look around any bar, mall or fast-food joint, and you’ll quickly find evidence of our collective corpulence. Spilling out of our seats and our relaxed-fit jeans, we cram together at tables to down mountainous plates of food and bucket-sized drinks. Doors have been widened to accommodate us, and chairs reinforced. Even our pets have grown plump, and, more tragically, our children.

According to the Centers for Disease Control and Prevention, one-third of Americans have progressed to that dangerous state of flabbiness known as obesity. Another third are overweight. This means that, all told, hundreds of millions of us now carry too many pounds, and with them, a greater risk for obesity-related illnesses, including diabetes, heart disease and some cancers, just to name a few.

On one level, there’s an obvious reason for our growing weight problems—and an obvious solution. We’re eating too much, and we need to eat less. But less of what, exactly? Should we cut out fats or cut back on carbs? Are we eating too much red meat or not enough? For every diet that works for one person, an opposing diet seems to work for someone else. And then there are those rare individuals who appear able to eat anything and never gain a pound. It seems like something else must be going on that explains our complex response to food, something beyond the matter of food itself.

We’ve always had nutritional experts who tell us about diets, but now we’re telling them how the diets work.

As it turns out, there is. Though we tend to see food as the cause of our flab, it’s the way food interacts with our intricate network of genes that ultimately dictates whether we pack on pounds. In the past several years, scientists have discovered dozens of obesity-related genes, including ones that control the size of our fat cells, our metabolic rate and how quickly we feel full. And while the story that’s emerging from these genes is wildly complicated, it may also finally produce solid answers to a crisis that has reached epidemic proportions.

At least that’s the hope of James Ntambi. A CALS professor of biochemistry and nutritional sciences, Ntambi has been working to unlock the secrets of how food interacts with our genes for more than 20 years. It’s a curiosity that began as an undergraduate student at Makerere University in his native Uganda. Ntambi can recall lingering outside the biochemistry department to pore over wall charts that detailed the body’s metabolic pathways. Eventually he turned his attention to fat cells—specifically, how the small, precursor fat cells we’re all born with transform over time into fat-storing adipose tissue. In the late1980s, Ntambi began to study a gene called SCD, which seemed to dramatically increase its activity during this conversion process, making him wonder about its potential link to obesity. He has been following that hunch ever since.

We now know that SCD encodes an enzyme that converts certain saturated fatty acids into unsaturated forms. These unsaturated fats are the building blocks of many types of lipids, including triglyceride, the main component of body fat. In the lab, Ntambi’s team showed that mice that lack the SCD gene are completely unable to store fat from food or make new fat from carbohydrate. Instead, they burn calories like crazy. Even when they eat the equivalent of a hamburger and fries at every meal, these mice gain virtually no fat.

Ntambi’s research with these miracle mice has sent drug companies scrambling to find chemicals capable of inhibiting the SCD genes in our bodies, which would supposedly allow us to eat fatty foods without storing extra fat. But intriguingly, Ntambi has found that certain foods and other biological molecules do the same thing. For example, omega-3 and omega-6 fatty acids—also known as fish oils because of their abundance in fish—naturally suppress SCD. In lab studies, fish oils cut the activity of the gene significantly, helping tip the body’s metabolism away from fat synthesis and storage and toward calorie burning. This is likely one reason fish are so highly touted in diets. (The American Heart Association recommends that people eat foods high in fish oils at least twice a week.) They actually alter a key gene’s operation.

“We’ve always had nutritional experts who tell us about diets,” says Ntambi, “but now we’re telling them how the diets work.”

Growing up on a Ugandan coffee and cotton plantation, Ntambi never imagined that he would study fat. When he entered graduate school at Johns Hopkins University, he put his interest in metabolism aside and pledged to study “an African disease.” He began investigating the parasites that cause African sleeping sickness, as well as a related scourge of cattle called ngana, all the while making plans to continue the research back home in Uganda.He laughs heartily now at the memory, because of course things didn’t turn out that way.

Instead, after earning his doctorate in 1985, Ntambi was invited to do what turned out to be his fateful research on human fat cells. His new post charged him to identify and clone the genes in mice that switch on as fat cells grow, which led him to SCD. In 1988, he became the first person to clone SCD, and soon afterward, he began examining the foods and other factors that affect the gene’s activity.

What Ntambi has discovered since is that, while molecules such as fish oils inhibit SCD and promote energy expenditure, many others do the opposite. For example, the hormones insulin and estrogen, the vitamins A and D, and the simple sugars glucose and fructose all boost SCD’s activity dramatically, suggesting that when they’re present, they encourage the body to make fat. And two of these substances—glucose and fructose—are more present within us now than ever before.

One of the chief reasons is the emergence of high fructose corn syrup, a sweetener made from corn. Low corn prices in the 1980s made the sweetener a low-cost alternative to cane sugar, leading soft-drink giants Coca-Cola and Pepsi to begin using it. At the same time, Americans were growing wary of fat in their diets, and the food industry responded with an array of reduced-fat products, many of them stoked with corn syrup to boost their flavor. Now, corn-based sweeteners are in everything from fruit drinks to baked goods to supposedly healthy items such as yogurt.