Lean and Hungrier

By Michael D. Lemonick Wednesday, Aug. 13, 2003
    • WAGNER PHOTOS /GETTY IMAGES

    Carnie Wilson talks with Montel Williams about her gastric-bypass surgery

    Like millions of less celebrated Americans, Carnie Wilson was not just fat. At 5 ft. 3 in. and more than 300 lbs., she was morbidly obese — more than 100 lbs. above her ideal body weight. After trying all sorts of diets that didn't work, the daughter of Beach Boy Brian Wilson and member of the now disbanded pop trio Wilson Phillips turned to a drastic last resort: gastric-bypass surgery. Doctors sewed up most of her stomach, reducing it to a tiny receptacle that holds several tablespoonfuls at best, and isolated much of her small intestine to reduce nutrient absorption. Result: filled to bursting after just a few swallows, she simply couldn't eat the way she used to. In three years, Wilson dropped an astonishing 150 lbs. What's surprising, though, is that she lost not just the ability to overindulge but also her appetite. "For the first year and a half," she says, "it was almost nonexistent. I had to remind myself to eat."

    Wilson's experience isn't all that unusual, and while doctors still aren't exactly sure what's going on, a report in last week's New England Journal of Medicine offers a tantalizing clue. The loss of appetite in bypass patients may be linked to a recently discovered gastric hormone called ghrelin. Not only that, ghrelin may turn out to be one reason we feel hungry in the first place and why it's so hard for dieters to keep weight off. Understanding how ghrelin works could even lead to effective weight-loss drugs or drugs to promote weight gain in anorexics and cancer patients.


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    For now, researchers are careful to emphasize only what they know for sure. Their study involved just 28 patients, and while the scientists came to three conclusions, lead author Dr. David Cummings of the University of Washington says, "I feel very solid about two of them." The first is that ghrelin levels in the bloodstream rise significantly before meals and drop afterward. This suggests that ghrelin is involved in triggering the desire to eat — and indeed, earlier studies performed since the hormone was discovered in 1999 have shown that a ghrelin injection just before a meal causes people to eat more than they normally would.

    The second conclusion reached by Cummings and his colleagues is that ghrelin levels are higher on average in people who have lost weight from dieting. "It's well known that your body works against you when you try and lose weight," he says. If your weight falls below a certain "set point," which varies from one person to the next, your metabolism adjusts to bring you back. "What's new," explains Cummings, "is the possibility that a rise in ghrelin is one way it's done."

    Cummings is less sure of the third conclusion, that bypass patients have only a quarter as much ghrelin as most people of normal weight. "It was based on only five people," he says, "and it's quite possible that had we studied a sixth, he would not show that." Still, the conclusion makes sense on its face. Ghrelin is produced mostly by cells in the stomach; if large parts of that organ are cut off from the rest of the digestive system, they may well stop churning out the hormone.

    But while it's tempting to think that ghrelin is a magic bullet that could be used to keep us all at a perfect weight, doctors think that's highly unlikely. Similar hopes were raised a few years ago for leptin, a hormone that acts as an appetite suppressant. After years of trying, nobody has found a way to make it into a useful medication, largely because patients quickly develop a leptin tolerance.

    What doctors suspect is that both leptin and ghrelin are part of a complex system of brain and body chemicals that have evolved over millions of years to govern weight and appetite. Says Dr. Rudy Leibel, an obesity expert and head of the molecular-genetics department at Columbia University: "It's just unlikely that any single component of this system will necessarily lead to a definitive therapeutic agent."

    That doesn't mean pharmaceutical weight control is forever out of the question. "In the next 10 years," says Dr. Bradford Lowell, an associate professor of medicine at Harvard and an expert on obesity, "we'll be able to determine the complete wiring diagram for body-weight control." And once scientists understand the entire system, not just a few of its components, they may be ready to design drugs that will make obsolete the drastic surgery that Carnie Wilson underwent.