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Appetite Hormone Doesn't Aid Weight Loss

Leptin curbs desire to eat, but men don't shed pounds in new study

FRIDAY, Sept. 21, 2001 (HealthDayNews) -- Leptin, the appetite hormone once hailed as a potential miracle treatment for obesity, has come up short in yet another weight-loss trial.

Obese men who received weekly injections of leptin were less hungry and had less of an urge to eat in the morning than men treated with dummy shots, but the obese group ended up shedding fewer pounds.

The findings don't necessarily mean leptin is worthless, experts say. But they do suggest that it's far from ready for deployment in the weight-loss wars.

"In order to get an effect on weight, we either need to give more leptin or be more clever about how we give it," says L. Arthur Campfield, a nutrition expert at Colorado State University and a co-author of the study, which appears in the October issue of the American Journal of Clinical Nutrition.

Too little of the hormone makes you hungry, while normal levels tell your body that enough's enough. As people gain weight, their fat cells generally produce more leptin, suggesting that the body develops resistance to it. In rare cases, people are born without the substance, and they, like the lab animals engineered to lack it, become extremely obese.

Supplemental leptin sparkled in trials of obese animals, producing dramatic weight loss and metabolic changes, experts say. Yet as the latest work and earlier, equally disappointing studies show, replicating those successes in overweight humans is harder than spurning a second helping of dessert.

Campfield was part of a team of scientists at the drug firm Hoffman La-Roche that invented a long-acting version of leptin. Roche, which funded the latest trial, has since put its leptin program on hold, as have other biotech firms that have been frustrated by the failure of the hormone to prove a "magic bullet" against obesity.

Instead, Campfield says, the pharmaceutical industry has shifted its focus from supplemental leptin toward compounds that help the body take better advantage of its supply of naturally occurring hormone, which is unquestionably important in appetite and weight.

Campfield and colleagues at Maastricht University in the Netherlands followed 30 obese men, whose average age was 44, with an average body mass index (BMI) of 34. BMI is a ratio of weight to height and is considered a better measure of obesity than pounds alone. A BMI of 34 -- that would be 240 pounds for someone 5 feet 10 inches tall -- is considered high risk for the adverse health effects of obesity, such as diabetes and heart and vessel disease.

For three months, half the men received weekly 20-milligram injections of leptin while the rest were given inactive placebo shots. All of the men were required to cut their energy intake to a modestly lightened diet of 2,100 calories a day.

Men who received leptin did show a significant and sustained drop in appetite and hunger when they woke up in the morning, while those who didn't get the hormone reported immediate and persistent increases in both urges, the researchers say. The hormone also appeared to suppress appetite and hunger throughout the rest of the day.

But by the end of the study, the men on leptin had lost an average of 9.5 pounds, while those on the placebo had lost an average of 14 pounds.

Campfield says the results may demonstrate that low doses of leptin affect appetite while higher doses lead to weight loss. "It looks like the first effect [of leptin] is to modulate appetite," Campfield says. "If you increase the dose, then you can start to have some effects on body weight."

Campfield says his group has conducted another study, due out soon, showing that 60-milligram shots of leptin produce weight loss about 20 to 30 percent greater than that from no treatment. At that dose, the drug continues to be well tolerated, he adds.

Still, Dr. Andrew Greenberg, director of the program in obesity and metabolism at Tufts University in Boston, says the latest work and other trials argue that "there's a good chance that [synthetic] leptin won't be used to induce weight loss" in people. That's surprising, he says, considering that the hormone has done so effectively in all manner of lower-order animals.

Like Campfield, Greenberg believes drugs that help the body use its own leptin more efficiently are probably the weight-loss therapy in the future. Even so, he adds, appetite and sensations of hunger aren't the only reasons people eat. Emotions, for example, play an important role in human food intake.

What To Do

To learn more about the dangers of obesity, visit this National Institutes of Health web site. To calculate your Body Mass Index, visit Shape Up America!

You can also try the National Heart, Lung, and Blood Institute or the American Heart Association.

SOURCES: Interviews with L. Arthur Campfield, Ph.D., director, food science and human nutrition, Colorado State University, Fort Collins; Andrew Greenberg, M.D., director of the program in obesity and metabolism, Tufts University, Boston; October 2001 American Journal of Clinical Nutrition
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