All this new research on the workings of body fat also has revealed why it's so hard to lose weight and keep it off: As you eat more, exercise less, and ratchet upward on the scale, your hormones adjust and fiercely guard the new status quo. For example, the amount of leptin—a hormone secreted by fat that regulates food intake and energy expenditure—circulating in your blood is proportional to the amount of fat you've got stored, says Christopher Newgard, director of the Sarah Stedman Nutrition and Metabolism Center at Duke University. When the hypothalamus of a person at a healthy weight sees a higher level of leptin than it expects, it tells the body to ease up on food intake and boost energy burning. Sounds great—perhaps you'd like to sprinkle some on your morning cereal? But researchers tested the supplement idea after leptin was discovered in 1994 and found that chronically high levels seem to desensitize the brain, so that leptin's ability to reduce food intake all but disappears.
Fat cells, moreover, don't seem to go away; while other cells are programmed to die, "you've bought them for life," says Robert Kushner, professor of medicine and obesity-care specialist at Northwestern University Feinberg School of Medicine. Thus, the goal of shedding pounds really is about slimming fat cells down, then keeping them from packing in triglycerides again.
The obvious question: How much work is necessary to succeed at trimming the fat? The American Heart Association and the American College of Sports Medicine issued an updated, joint set of guidelines in August on physical activity. To "promote and maintain health," 30 minutes of moderate activity five days per week will do the job. But to prevent weight gain or shed pounds, "more is better." In fact, much more is called for: from 60 to 90 minutes of physical activity on most days.
The amount and type of food you take in matter, too, of course—although researchers don't yet understand how (or how well) various diets and interventions work. At Duke, for example, multiple ways of shedding pounds are being studied—from the Atkins Diet to bariatric surgery to drug treatments—to clarify what they do to a person biochemically and why certain people have success and others flounder. The one trick that researchers can agree upon so far is both simple and painfully familiar: Eat less and move more.
For Jesse Manek, that meant ditching what he craved most: fast food, ice cream, and sugary foods. In his doctor's mind, the ever present sweetener fructose, which shows up in everything from pasta to sports drinks to soda to breads, is the refined carbohydrate most culpable in the rise of obesity. Its breakdown in the liver, says Lustig, promotes inflammation, hypertension, and insulin resistance. The extra fiber Manek gets by stocking up on fruits, vegetables, and whole grains helps control his insulin levels and makes him feel fuller, longer. Thanks to his vigorous exercise regimen, he says, an irony has unfolded: "I actually eat more now."
With Katherine Hobson
Corrected on 1/9/07: An earlier version of this article misstated the name of the American Institute for Cancer Research.