A hormone that makes the body think it's fat appears to help people keep their weight down, and now scientists think they've figured out why. When dieters shed pounds, they also lose leptin, and new findings indicate that the hormone may be needed for nervous system behaviors that prevent the pounds from returning.

Every dieter knows how hard it is to keep those pounds off. When people lose weight, the body fights back by increasing appetite and using energy more efficiently, leaving more calories to store. Leptin may be to blame. Once hailed as a natural hormone that might help people slim down, leptin fell out of favor when researchers found that injecting it did not cause obese animals to lose weight. But, rather than helping people shed pounds, the hormone may keep those pounds from returning. Previous work by endocrinologist Michael Rosenbaum and colleagues at Columbia University College of Physicians and Surgeons in New York City found that, when injected into a small group of dieters, leptin reversed some of the physiological changes that stimulate weight gain, such as drops of thyroid hormone levels in the blood.

In the new study, the team further investigated leptin's effect on dieting bodies. The researchers began by sequestering seven obese and three lean volunteers in a hospital for 6 to 9 months. All volunteers went on a liquid diet that caused them to lose 10% of their initial weight; the researchers then limited their calorie intake to maintain this weight. At first, Rosenbaum's team found that these dieters resembled many others in their energy expenditure: When placed on a stationary bicycle, the volunteers' muscles were 20% more efficient at using energy than at their original weight, and they experienced about a 40% loss in adrenaline. But giving them booster shots of leptin reduced the efficiency with which their muscles used energy to predieting levels and restored the volunteers' adrenaline production. By restoring these physiological functions to their prediet state, leptin appears to fool the body into thinking that it is at its normal weight and keeps it from fighting back against fat loss, the researchers report in December's Journal of Clinical Investigation.

"This study suggests leptin might be useful in maintaining weight loss, not causing it," says endocrinologist Rexford Ahima of the University of Pennsylvania School of Medicine in Philadelphia. "I hope these results will open the doors to studying [leptin replacement] with weight-reduction programs."