Leptin Works on Brain Before and After Birth

Studies shed light on activity of appetite hormone

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HealthDay Reporter

THURSDAY, April 1, 2004 (HealthDayNews) -- Leptin, the hormone that helps regulate body weight, can affect brain structure and function before birth and in adulthood, two research teams report.

The findings don't swing open a door to the magic diet pill that has been hoped for since leptin was discovered a decade ago, members of both research groups said. But they do add significantly to knowledge about just what it is that leptin does.

"This work is at the most basic level, where the function of leptin was not thought to occur," said Richard B. Simerly, a senior scientist at the Oregon National Primate Research Center and a member of one research team. "Now we can think about it."

Both groups report their results in the April 2 issue of Science, and both worked with a strain of mice bred to lack the gene for leptin.

Simerly and his colleagues looked at what happened to the brains of unborn mice when their mothers were given leptin during pregnancy. Without leptin, the part of the brain devoted to appetite regulation is shrunken. With leptin, that brain segment develops as it does in normal mice.

Since leptin production is a function of diet, Simerly said, "this clearly has implications that things like maternal diet alter levels of leptin, and it is possible that these changes can permanently predispose to obesity."

There still is no proof that what happens in laboratory mice happens in humans, he said. Still, epidemiological studies in India indicate that very low birth weight babies are likely to become obese when they eat a fat-rich Western diet, Simerly added.

"One possible interpretation is that when there are low leptin levels in utero, you end with a brain that is less sensitive to leptin," he said.

The second finding, from researchers at Yale University and Rockefeller University, seems to argue against leptin playing a predestined role in obesity. They are reporting that leptin can change the wiring of the brain in adult mice, inhibiting activity of brain cells that encourage the animal to eat and activating cells that curtail feeding. It is part of an ongoing revolution in neurology in which the adult brain, until recently thought to be unchangeable, has been found to be anything but that.

"The bottom line of our paper is that in the brain, connectivity is extremely plastic, not hard-wired, and that the brain is constantly rearranging itself," said Dr. Tamas L. Horvath, an associate professor of obstetrics, gynecology and neurobiology at Yale and a member of the research team.

The scientists now "are trying to figure out how we could change the wiring in obese people," Horvath said. "We're trying to understand the mechanism that enables this plastic rearrangement to occur."

It isn't a simple question to answer, since other molecules, including gherlin, a hormone that stimulates appetite, also get into the act. What is clear, Horvath said, is that "brain plasticity is a critical element in the appropriate management of food intake."

While one study seems to say leptin levels during pregnancy can determine obesity in adult life and the other argues for a dynamic, changing effect in adults, there is no conflict between the two findings, Simerly said. He compared the brain circuitry involved in appetite control with the wiring system used to bring cable television into the home.

"The effect during fetal development is to determine how many cables are laid down into a city," Simerly said. "Later, the effect is on the finer details of distribution of wiring within a city; how many wires go into a home."

More information

In the absence of a miracle pill, you can get advice on fighting obesity from the National Heart, Lung, and Blood Institute. Learn about leptin from the Duke Weight Loss Surgery Center.

SOURCES: Richard B. Simerly, Ph.D., senior scientist, Oregon National Primate Research Center, Beaverton; Tamas L. Horvath, D.V.M., Ph.D., associate professor, obstetrics, gynecology and neurobiology, Yale University, New Haven, Conn.; April 2, 2004, Science

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