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Obesity Brains
July 22, 2005
By Stacey Young

A hormone that stops us from eating too much could affect other addictions as well. As this ScienCentral News video explains, that's the conclusion of researchers studying people born without the hormone who got replacement therapy.

Overeating in the Brain

The researchers looked at brain scans to see leptin activity in the brain before and after treatment.

If you've ever uttered the words, "I'm so hungry I could eat a horse," you know it's not literally possible to chow down on such a huge animal in one sitting. But have you ever considered what stops us from being able to do so (besides the scarcity of horsemeat on most menus)? Scientists say a number of hormones are at work in alerting us that we've had enough to eat.

Now there's fresh evidence that one of those hormones—leptin—may alter brain structure in areas associatedwith craving and addiction in obese individuals born without a gene that produces leptin.

The researchers looked at brain scans to see leptin activity in the brain before and after treatment.

"There are very few people who have a genetic mutation, that they are just born without it…they tend to eat too much," explains Julio Licinio, a biobehavioral researcher at UCLA who, along with a team of UCLA scientists, studied the only three such people scientists have identified as lacking the leptin gene. Licinio gave them daily leptin replacement while his colleague, brain researcher Edythe London, used MRI brain scans to look at the volunteers' brain structure before they took leptin, and then at three and 18 months into the study.

"We found dramatic results in brain structure," says London. "The actual composition of the brain changed, but it wasn't all over the brain. The composition of the brain changed only in regions known to be related to self control behaviors."

The team reported in the Journal of Clinical Endocrinology and Metabolism that the volunteers not only lost 50 percent of their body weight without the aid of dieting, but also had significant changes in gray brain matter—the wiring that allows brain cells to signal the body and each other—in the inferior parietal lobule, the cerebellum on the left side of the brain and in the anterior cingulate gyrus.

"The anterior cingulate gyrus is particularly interesting," says London, who has published a number of studies on addiction and the brain. "That's because the anterior cingulate gyrus repeatedly is turned on in brain imaging studies for craving of other substances: drugs of abuse, cocaine, tobacco. So we believe that there's a commonality, between craving food, hunger, craving for drug—and that leptin may have a fundamental role in all these types of behaviors."

For now, London admits to being stumped as to how the brain changes she saw might be linked with cravings: "It's very hard to know what a structural change like increase in gray matter could mean. It could mean that the nerve cells in that part of the brain are larger. It could mean that the connections have changed in that area of the brain."

And she says she's not even sure leptin was acting in the brain to cause the changes: "Leptin may have had an effect somewhere else in the body and some other factor may have come into the brain to produce the effects."

Further study will most likely uncover more; something London says is key to helping people with food addictions. "If we understand the biology of addictive disorders, it goes beyond dealing with anybody that has a very unique problem with cocaine, methamphetamine or heroin. It begins to extend to a family of disorders that include control of food."

But before looking to leptin to help you loosen your belt, London says to keep in mind the unique nature of this study group: "We know that leptin has dramatic affects to reduce weight loss in a genetically deficient population who don't make leptin on their own, but there is a lot of variability in the general population. Prior studies where leptin was used by itself to treat obesity were not very successful."

Still, she says the findings "give us some clues, and we have to explore the interaction between genetics and environment in modulating body weight."

So for now, if you're looking to fit into that fabulous new wardrobe you'll have to do it the old-fashioned way…with a good diet and a lot of self-control.

This research was published in February 15, 2005 issue of the Journal of Clinical Endocrinology and Metabolism and was funded by the National Institutes of Health.

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