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Researchers discover molecular 'switch' that tells body to store or burn fat

identified by Friedman's group in 1995. Friedman and his colleagues showed that leptin is a fat cell hormone that functions as a nutritional signal to regulate body weight, metabolism and other physiologic processes.

Since the discovery of leptin, Friedman and other scientists have been searching for other components of the biological system that control body weight. The Rockefeller and University of Wisconsin researchers now hypothesize that leptin acts in part by suppressing SCD-1's activity, which in turn activates a metabolic pathway that promotes the burning of fat. Previous research by Friedman's Rockefeller group and other scientists showed that lipids, or fats, in specific body tissues, including the liver, were elevated in leptin-deficient mice and humans and decreased when they received leptin treatment.

The scientists who conducted the Science study, including researchers from the Rogosin Institute in New York City, used "gene chip" technology, which enables researchers to study thousands of genes at one time, to identify genes that leptin regulates in the liver. Co-author and Rockefeller scientist Nicholas Socci, Ph.D., developed a computer program to sift through some 6500 mouse genes contained in a single Affymetrix Inc. gene chip. The researchers looked for genes that are specifically suppressed by leptin, and SCD-1 topped a final list of 36 genes.

"Gene chips identify hundreds of genes that are potentially important, and we wanted to do something to prioritize that list for further follow up," says Cohen. "Nicholas wrote a software program to rank the genes based on the extent of their response to leptin with the idea that some or all of these genes might be required for development of obesity."

SCD-1 is an enzyme that is required for the synthesis of palmitoleate and oleate, the major monounsaturated fatty acids found in triglycerides in fat cells. These monounsaturated fatty acids are generated from saturated fatty a
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Contact: Joseph Bonner
bonnerj@mail.rockefeller.edu
212-327-8998
Rockefeller University
11-Jul-2002


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