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Findings by Einstein scientists reveal possible strategy against obesity, diabetes and infertility

(BRONX, NY) Twelve years ago, scientists discovered leptin--the now-famous hormone that controls appetite, burns calories and performs other crucial physiological activities as well. But the precise mechanism(s) by which leptin carries out these metabolic tasks is still controversial. Now, researchers at the Albert Einstein College of Medicine of Yeshiva University have shown how leptin exerts some of its most important effects.

Their findings, reported in the July 5 issue of Cell Metabolism, suggest a novel approach for duplicating leptin's actions when the body no longer responds to the hormone.

Fat cells release leptin into the bloodstream. The hypothalamus "reads" the amount of circulating leptin and uses this information to regulate appetite, metabolism and other processes. "Leptin is known to bind to cell-surface receptors in the hypothalamus and then to activate various other cellular signals including a molecule called STAT3--but the role of STAT3 in mediating leptin's multiple physiological effects was still unknown," says Dr. Luciano Rossetti, the study's senior author and the director of the Diabetes Research and Training Center at Einstein.

To learn whether STAT3 mediates some of leptin's activities, "we devised a technique for inactivating STAT3 with pinpoint accuracy in the hypothalamus and observing the results in laboratory animals when we administered leptin," says Dr. Rossetti. "Our tool for rapidly inactivating STAT3 was a cell-permeable peptide (short protein) that we infused into specific areas of the hypothalamus using fine needles. This technique can serve as a model for investigating all types of signaling pathways in selective regions of the brain."

The researchers found that STAT3 production is essential for leptin's best-known action: acutely reducing food intake. Since obesity occurs when people become resistant to leptin's "curb your eating" message, this finding suggests that bypassing leptin and
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Contact: Karen Gardner
kgardner@aecom.yu.edu
718-430-3101
Albert Einstein College of Medicine
5-Jul-2006


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