Five Stealth Forces in Weight Loss

Scientists are zeroing in on the unexpected ways molecular forces—including genes and viruses—impact your weight. In the process, they're upending the conventional wisdom on just what makes a successful diet.

By Sora Song, published on July 01, 2008 - last reviewed on September 23, 2008

The field of weight loss is like the ancient fable about the blind men and the elephant. Each man investigates a different part of the animal and reports back, only to discover their findings are bafflingly incompatible.

The various findings by public-health experts, physicians, psychologists, geneticists, molecular biologists, and nutritionists are about as similar as an elephant's tusk is to its tail. Some say obesity is largely predetermined by our genes and biology; others attribute it to an overabundance of fries, soda, and screen-sucking; still others think we're fat because of viral infection, insulin, or the metabolic conditions we encountered in the womb. "Everyone subscribes to their own little theory," says Robert Berkowitz, medical director of the Center for Weight and Eating Disorders at the University of Pennsylvania School of Medicine.

But within this fractured tableau, a few patterns now stand out clearly. A consensus is emerging that the conventional wisdom—eat less, exercise more—is inadequate at best. A quick look at our collective waistline makes it painfully clear the old equation—calories in minus calories out equals weight change—is fundamentally flawed. Research shows not every calorie is created equal, and different bodies use calories in different ways. We're programmed to hang onto the fat we have, and some people are predisposed to create and carry more fat than others. Diet and exercise help, but in the end the solution will inevitably be more complicated than pushing away the plate and going for a walk. "It's not as simple as 'You're fat because you're lazy,'" says Nikhil Dhurandhar, an associate professor at Pennington Biomedical Research Center in Baton Rouge. "Willpower is not a prerogative of thin people. It's distributed equally."

Science may still be years away from giving us a miracle formula for fat-loss. Until then, it's up to us, one paunchy individual at a time, to shed our extra flab. It's easier said than done, especially since we may have been doing it wrong all this time. But the newest, most unexpected findings from the front lines of diet research may yet help tip the scales in your favor.

Evolution: Your Body Wants You to be Fat

If you've ever tried to lose weight—be it 5 pounds or 50—you don't need to be told the human body resists weight change. We're each born with a predetermined set point—a weight range that typically spans about 10 to 20 pounds—and the further we push our weight away from it, the more intensely the body fights its way back. Hence the yo-yo effect: You diet and lose weight, only to gain it all back once you stop your diet. The culprit isn't lack of willpower, it's evolution.

The command center for the body's weight-management system resides in the hypothalamus—and it's calibrated to favor the preservation, rather than the elimination, of fat. That's accomplished through the hormone leptin, a crucial player in the brain's weight-management circuitry. Leptin is produced by the body's fat cells and signals the brain to regulate appetite and satiety—and, therefore, weight. If you lose body fat and leptin, it triggers hunger and the urge to eat; if you gain fat and increase leptin, you eat less. The more leptin your body produces, the leaner you tend to be; the less leptin you make, the higher your set point and the fatter you stay. Voila, the secret to set-point maintenance.

But things don't always go according to plan. The regulatory system can go awry: Some people produce too little leptin; others become desensitized to it. And when obese people lose weight, their leptin levels plummet along with their metabolism. The body becomes more efficient at using fuel and conserving fat, which makes it tough to keep the weight off. Obese dieters' bodies go into a state of chronic hunger, a feeling Rudolph Leibel, an obesity researcher at Columbia University, compares to thirst. "Some people might be able to tolerate chronic thirst, but the majority couldn't stand it," says Leibel. "Is that a behavioral problem—a lack of willpower? I don't think so."

Then what is it? In short, DNA. How the body maintains its regulatory mechanism may be largely under the influence of genes. According to some researchers, 70 percent of variation in people's weight may come from defects on genes, and many of those genes act on a common hunger-satiety pathway in the hypothalamus. One such gene is the melanocortin 4 receptor (MC4R), which communicates with leptin and triggers a feeling of fullness. When MC4R malfunctions, it causes overeating and obesity in animals and humans. Researchers estimate 6 percent of obese children and adults can trace their condition to a genetic defect that interferes with MC4R. But genes aren't destiny. When MC4R is disabled in mice, it causes overeating and obesity—unless they're allowed to exercise early on. In the end, weight is the result of a subtle dance between genes and environment.

Exercise: Why the Evening Walk Isn't Enough

The government has long espoused moderate daily exercise—of the evening-walk or take-the-stairs variety—but that may not do much to budge the needle on the scale. A 150-pound person burns only 150 calories on a half-hour walk, the equivalent of two apples. It's good for the heart, less so for the gut.