Hormone may help dieters keep weight off: U.S. study

By Julie Steenhuysen
21 june 2008--Falling levels of a hormone called leptin that helps the brain resist tempting foods may explain why people who lose weight often have a hard time keeping it off, U.S. researchers said on Friday.
Restoring leptin to pre-diet levels may reverse this problem, they said, offering a way for weary dieters to finally win the weight battle.
"When you lose weight you've created about the perfect storm for regaining weight," said Michael Rosenbaum of Columbia University Medical Center in New York, whose research appears in the Journal of Clinical Investigation.
After weight loss Rosenbaum said the metabolism not only becomes more efficient, so the body needs fewer calories, but the brain becomes more vulnerable to tasty-looking treats.
"Areas of your brain involved in telling you not to eat seem to be less active. You are more responsive to food and you are less in control of it," he said in a telephone interview.
Leptin is a natural appetite suppressant secreted by fat cells in the body. Its discovery created a stir in the 1990s when researchers found leptin caused mice to eat less and lose weight. This rarely happens in humans.
Since then researchers have been looking the best way to use the hormone to help treat obesity.
In earlier studies, researchers found that when people lose weight, leptin levels fall as the body tries to protect its energy stores.
Rosenbaum investigated the impact of this loss of leptin on the brains of people who had lost weight, and whether replacing the hormone might help them keep off the weight.
He used an imaging technique known as functional magnetic resonance imaging that shows activity in the brain. The researchers studied six obese patients before and after going on a hospital-supervised diet that reduced their body weight by 10 percent.
People were shown pictures of food and non-food items, such as an apple or a yo-yo. The researchers found that after weight loss, areas in the brain responsible for regulating food intake were less active when people were shown food images. Areas in the brain responsible for emotion were more active.
When the researchers restored leptin to the levels before the dieting, these changes were largely reversed.
Similar results have been seen in people with a rare genetic condition in which their bodies do not make leptin.
Rosenbaum believes leptin could be a useful tool in helping people maintain weight loss. "The idea is there should be a whole new class of therapies to help us keep weight off after we have lost it," he said.

Brain scans of obese show hunger hormone at work

By Maggie Fox, Health and Science EditorMon Oct 29, 6:21 PM ET
Giving the body's natural appetite suppressant to morbidly obese volunteers de-activated their brain's response to tasty food -- and the new brain activity lasted for as long as the hormone was delivered, U.S. researchers reported on Monday.
They said their imaging tests show some of the brain circuits activated by leptin, a hormone that helps control appetite, and may lead to new and better treatments for obesity, the researchers wrote in their report, published in the Proceedings of the National Academy of Sciences.
"While they were off leptin they got really hungry when they saw pictures of high-calorie food, and that was associated with high activation in a part of the brain that is related to food craving," said Edythe London of the University of California Los Angeles, who led the study.
With leptin, the executive centers involved in self-control were more activated. "The findings suggest that leptin strengthens the executive centers," London said in a telephone interview.
The discovery of leptin in the 1990s created a furor, because when injected into rodents it caused them to eat less and lose weight. But the same rarely occurs in humans.
So experts are trying to find out how it works in people and find ways to better harness its effects.
London and colleagues examined three members of a family with a rare genetic defect that causes their bodies to produce no leptin. Such people become extremely obese.
Earlier studies had shown that when injected with leptin, these people lose up to 50 percent of their body weight -- unlike most people, who usually continue to over-eat even when injected with leptin.
London wanted to see what was going on in their brains.
"In 2005 we found that leptin actually changes the structure of their brain," London said in a telephone interview. They found the area of the cerebral cortex involved in self-control actually grew after repeated leptin administrations.
But they wondered what else was going on.
They set up an experiment using functional magnetic resonance imaging, a type of brain scan that can see the brain's activity in real time. They recorded the brain activity before and after giving leptin, a study that continued for two years.
Pictures of food treats got the brain busy.
But different areas of the brain lit up with and without leptin, they reported.
One surprise was the activation of the cerebellum -- a section of the brain at the base of the head.
"Although the cerebellum has not traditionally been linked with eating behavior, it is thought to play a role in reinforcement and drug craving," they wrote.
"With leptin supplementation, the cerebellum showed enhanced activation," they wrote.
London said she is not sure what to make of this.