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Fat hormone leptin alters brain architecture and activity, which in turn drives feeding behavior

c connections, and recordable changes in the electrical activity of specific brain cells.

Other researchers have shown that brain maps of cells can be quite plastic or changeable. Pinto, whose scientific training is in the area of learning and memory, wanted to know if the same was true when it came to feeding behavior.

"Feeding turns out to be a really good model to test plasticity because it's much simpler to study than the system that controls learning or memory," said Pinto.

For her research, Pinto used a famous mouse strain that resembles obesity in some humans. These mice lack leptin and grow to twice the size of a normal mouse with a body that contains five times the fat.

Using the obese mice, Pinto and her colleagues were able to show effects of the hormone on two particular sets of neurons: NPY and POMC. These neurons are found in the hypothalamus, an area of the brain that controls appetite. NPY stimulates food intake and increases body weight while one of the active products of POMC, a peptide called alpha-MSH, has the opposite effect. Pinto and colleagues discovered that leptin changes the number of connections that either excite or inhibit NPY and POMC neurons in the hypothalamus.

Led by Roseberry, the researchers also showed that leptin alters the electrical activity of the connections to NPY and POMC neurons. These effects are consistent with what the researchers found on the structural level.

In other words, leptin inhibits NPY neurons that encourage the animal to eat and reserve energy. At the same time the hormone activates POMC neurons that curtail feeding. And it does this by altering the synaptic inputs of these cells -- the points where the cells connect and communicate.

The Rockefeller scientists suggest that these leptin-induced structural and functional changes are responsible for changes in the animal's behavior, too.

Six hours after administering leptin to obese mice, ch
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Contact: Lynn Love
lovel@rockefeller.edu
212-327-8977
Rockefeller University
1-Apr-2004


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