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Signaling path in brain may prevent that 'I'm full' message, UT Southwestern scientists discover
Date:3/1/2011

DALLAS March 1, 2011 Researchers at UT Southwestern Medical Center have identified a signaling pathway in the brain that's sufficient to induce cellular leptin resistance, a problem that decreases the body's ability to "hear" that it is full and should stop eating.

"Leptin resistance is a significant factor, yet the mechanisms that underlie the problem remain unclear," said Dr. Joel Elmquist, professor of internal medicine and pharmacology at UT Southwestern and senior author of the study appearing in the March issue of Cell Metabolism. "The fact that this cellular pathway may be involved is a novel observation."

Leptin is a hormone released by fat cells that is known to indicate fullness, or satiety, in the brain. If the body is exposed to too much leptin, however, it will become resistant to the hormone. Once that occurs, the body can't "hear" the hormonal messages telling the body to stop eating and burn fat. Instead, a person remains hungry, craves sweets and stores more fat instead of burning it.

Leptin resistance also causes an increase in visceral, or belly, fat, which has been shown to predispose people to an increased risk of heart disease, diabetes and metabolic syndrome.

For the current study, the researchers induced leptin resistance in organotypic brain slices from mice. This research technique, used commonly in neuroscience, enabled the researchers to maintain the cellular and anatomical relationships and some of the network connections that normally exist within the brain.

"We're not dispersing cells. We're leaving them in a microenvironment that simulates what's going on in the brain," Dr. Elmquist said.

When the researchers began manipulating the network known as cAMP-EPAC pathway they found that activating this previously unexplored signaling avenue is enough to induce leptin resistance within hypothalamic neurons, a critical site of leptin action. They also found that when
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Contact: Kristen Holland Shear
kristen.hollandshear@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert

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