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

Scientists at the Howard Hughes Medical Institute and The Rockefeller University in collaboration with investigators at Yale University have found that leptin --- a hormone found in fat tissue and critical to regulating weight -- affects both the architecture and function of neural circuits in the brain.

The research is published April 2 in Science. Studies were conducted by Shirly Pinto, Ph.D., and her colleagues Aaron Roseberry, Ph.D., and Hongyan Liu, Ph.D., postdoctoral fellows in the Laboratory of Molecular Genetics headed by Jeffrey Friedman, M.D., Ph.D., at Rockefeller, in conjunction with Tamas Horvath, D.V.M., Ph.D. and his colleagues at Yale University.

The Rockefeller scientists discovered that leptin acts by changing the wiring of the brain, a phenomenon known as plasticity. The hormone alters the wiring by controlling synapses -- the inputs and outputs to neurons that, in this case, regulate feeding behavior.

"This is a very dynamic effect that's quite dramatic and somewhat surprising," said Friedman, a Howard Hughes Medical Institute investigator. "In response to leptin, the cells create new connections."

Treatment with leptin reduces weight in some individuals but not in others. So learning more about the hormone's mechanism of action could be critically important in understanding why some people are resistant to leptin's weight reducing effects. "The malleability of these feeding circuits by leptin suggest the possibility that the brain's wiring may be different in lean versus obese individuals," Friedman added.

In March 2004 the U.S. Centers for Disease Control and Prevention announced that obesity is now the second leading cause of death in the United States. Poor diet and inactivity now account for more than 400,000 deaths a year, second only to tobacco as a preventable cause of death.

Pinto and her colleagues have shown for the first time that leptin induces visible changes in the synapti

Contact: Lynn Love
Rockefeller University

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