Another newly discovered family of genes makes compounds called uncoupling proteins, which allow people to convert excess fat into heat instead of storing it. Researchers have shown that animals with high levels of these proteins do not gain weight as easily as those with lower levels.

People with the same weight, height, and basic shape

 may burn dramtaically different amounts of energy.

Each obesity-related gene affects a different aspect of weight control. For example, one gene might determine how quickly the gut lets the brain know that it is full. Another might dictate how effectively the body turns extra calories into body fat. There’s a genetic component to how much fuel muscles need just to get through a sedentary day. And genes also lie behind a tendency that some people have toward spontaneous physical activity—fidgeting, toe tapping, hair twirling—which burns up a substantial number of calories.


WHY DIETS DON'T WORK

Despite the role genes play in making people fat against their will, diet and exercise remain significant factors. As any dieter knows, losing pounds is never easy. That’s because the body uses a remarkably efficient set of tricks to keep fat at a stable level. Researchers refer to this stable level as the set point. When people successfully lose weight, their bodies undergo a change in metabolic rate that may seem counterintuitive. For example, participants in one study who held their weight at 10 percent below their set point showed a 15 percent drop in daily energy expenditure. Their bodies slowed down energy use to counteract the pounds they had lost. Researchers find this shift in metabolism to be just as marked after a weight gain too. In the same study, subjects who increased their weight showed 10 to 15 percent increases in metabolism.

So if our bodies are so good at maintaining a set point, why do people get fat at all? William Ira Bennett, a doctor at Cambridge Hospital in Massachusetts, recently wrote in the New England Journal of Medicine that although our bodies continue to defend their set points, external factors, such as habitual levels of physical activity and the composition and tastiness of diets, can reset them. Bennett believes that over time a sedentary life and the mere availability of rich, palatable food will slowly increase the weight the body is geared to defend. Because of genes, some people are more susceptible to a change in set point than others. They will always have more trouble keeping off any weight they lose through dieting. —S. V.

 It is now widely accepted among weight researchers that a person’s particular complement of genes determines what activities make him or her susceptible to weight gain as well as how strong that susceptibility is. The bottom line is that genes alone don’t make people fat. All of us simply have a greater or lesser genetic tendency to gain weight. Those with the strongest tendency—the worst combination of genes—are almost guaranteed to join the minority of people who weigh 300 pounds and up. The rest lie somewhere on a continuum that extends all the way down to those lucky people who can eat all the doughnuts they want and never need to punch a new hole in their belts.

What’s more, even if two people seem to have roughly the same tendency to gain weight, they may do so for different reasons, simply because of genetic variety. In 14 years of work at the National Institute of Diabetes and Digestive and Kidney Diseases in Phoenix, obesity researcher Eric Ravussin (now at Eli Lilly in Indianapolis) recently uncovered some fascinating examples. He looked at the differences in how people burn energy and how those differences contribute to weight gain. The work made him appreciate how widely metabolic rates can vary.

In a study of more than 500 volunteers, Ravussin and his colleague Pietro Tataranni analyzed resting metabolic rates—how much energy the body uses when it’s just trying to maintain the status quo. The researchers gathered this information using a clear plastic ventilated hood that looks like something out of a viral-scare movie. It fits snugly around a subject’s neck, continuously drawing in and siphoning off air. The wearer must lie awake for 40 minutes without moving. By measuring how much oxygen he consumes and how much carbon dioxide he breathes out, researchers can determine how much energy the subject spends on such basic functions as temperature control and involuntary muscle activity. Ravussin and Tataranni found that some of their volunteers burned as few as 1,067 calories a day, while others burned as many as 3,015.

A woman performs water aerobics at a North Carolina diet and fitness center. While most weight-loss programs involve exercise, its effectiveness can vary dramatically from person to person.

Contrary to what many people think, Ravussin says, a slow metabolism doesn’t necessarily go hand in hand with weight gain. “Most obese patients will tell you, ‘I have something wrong with my metabolism,’” he says. “And I believe that something is wrong. But it may not be their metabolic rate.” When Ravussin has measured rates, he has found that people with the same physical characteristics—same weight, same height, same basic shape—may nevertheless burn dramatically different amounts of energy each day.

Other researchers have shown that exercise has remarkably different effects on different people. When people exercise regularly for three to four months, their bodies can change dramatically: their hearts and muscles get stronger, and they can exercise harder for longer periods. But that is not true for everyone. When exercise physiologist Claude Bouchard of Laval University in Sainte-Foy, Quebec, put a group of 47 young men on a training program for 15 to 20 weeks, he found that some showed 100 percent improvement in their maximal oxygen uptake—a measure of how efficiently lungs, heart, and circulation can dispense oxygen to tissues crying out for it. Other men, however, showed almost no change. Bouchard has seen the same lack of effect on other measurements of how people adapt to exercise, such as heart size, muscle fiber size, and how much work people can perform in 90 minutes. “We believe that it is quite remarkable,” he says, “that for all the determinants that have been considered in a series of investigations performed in our laboratory, one can find nonresponders—even after 20 weeks of regular exercise at a frequency of five times a week over the last several weeks of the program.”

When it comes to weight, it has long been our habit to group heavy people together as if they all suffer from the same condition and should respond to the same cure. Every diet-and-exercise program is pitched as a one-size-fits-all remedy. As scientists begin to understand how different bodies control weight, they are learning to characterize various types of obesity and treat people accordingly. To many researchers and pharmaceutical companies, that treatment means drugs. By one recent count, 62 new compounds for treating obesity are currently in various stages of testing and development. “I expect we’ll see something like one or two new drugs being submitted to us every year for the next five to ten years,” says Leo Lutwak, a medical officer with the FDA’s Center for Drug Evaluation and Research.

CAN A VIRUS MAKE YOU FAT?

Biologists have found a virus that causes obesity in laboratory animals, such as chickens and mice. Now the researchers are testing people for it.

Although the idea sounds more like the premise of a B movie than scientific theory, two scientists at the University of Wisconsin in Madison believe they’ve found a virus that causes some people to get fat. Nikhil Dhurandhar and Richard Atkinson reported recently that when they injected a virus known as AD36 into mice and chickens, the animals’ body fat increased. Because humans were unlikely to volunteer for such experimentation, the scientists decided to test for the presence of antibodies to the virus. Of 154 people tested, about 15 percent of those who were obese had the antibodies. None of the lean people did.

However, the findings don’t necessarily prove that the virus caused obesity in the test group. As several virologists have pointed out, obese people may simply be more susceptible to such a virus. Still, in recent years researchers have been surprised to find that viruses can be linked to so many diseases that had been thought to have other origins. For example, viruses are now implicated in several types of cancer, hardening of the arteries, and even mental disorders such as depression. In addition, five viruses besides AD36 have already been shown to cause obesity in animals. The good news is that the same methods that produce flu shots each year could ultimately be used to create an antiobesity injection. —S. V.

These include the family of so-called exercise pills, drugs designed to boost the rate at which bodies burn fat and dissipate the energy as heat—an effect that would provide many of the benefits of regular mild exercise. Other pharmaceutical approaches use leptin and related molecules to tell the body that its fat stores are already ample, or target the chemicals in our brains that control appetite. Other pills prevent our bodies from absorbing some of the fat that we eat.

But even without new drugs, knowledge of the differences between bodies can lead to more thoughtful ways of dealing with weight. For example, some people tend to have less fat than most of us. As a result, when these people are exposed to a high-fat diet, they gain weight more readily. For them, cutting down on fatty foods might be a far easier and more effective way to maintain weight than, say, embarking on a vigorous exercise program. Ultimately we will be forced to accept that each person’s weight is as much a mark of his individuality as his face. And that could make weight really interesting.