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

An enzyme called SCD-1 plays a crucial role through the hormone leptin in signaling the body to either store fat or burn it, report a team of scientists in the July 12 issue of the journal Science.

The researchers, led by Jeffrey M. Friedman, M.D., Ph.D., a Howard Hughes Medical Institute investigator at The Rockefeller University, and James M. Ntambi, Ph.D., at the University of Wisconsin at Madison, showed that obese (ob/ob) mice, which lack the hormone leptin, lost weight by burning calories, when genetically crossed with a strain of mice carrying a mutation in SCD-1.

The missing SCD-1 enzyme also corrects a major clinical problem called fatty liver, which is found in leptin-deficient mice and several clinical settings in humans. These new findings point to a potentially novel strategy for treating obesity and fatty liver and add important new information concerning the mechanism by which leptin regulates body weight and metabolism.

Obese, leptin-deficient mice with mutations in SCD-1 lost weight despite continuing to overeat.

"Leptin causes weight loss by reducing food intake and by increasing energy expenditure. It is both surprising and important that a deficiency of SCD-1 reduced obesity by increasing energy expenditure without affecting food intake at all," says first author Paul Cohen, graduate student in the joint Tri-institutional M.D.-Ph.D. Program of Rockefeller, Weill Medical College of Cornell University and Sloan-Kettering Institute.

"SCD-1 appears to be an important control point and may function as a switch determining whether fat is stored or burned," adds Friedman, professor and head of laboratory at Rockefeller.

Leptin and SCD-1 are members of a complex metabolic pathway that governs the body's propensity to burn fat. The ob gene, which codes for leptin, was isolated in 1994 by Friedman's HHMI laboratory at Rockefeller. Leptin, named after the Greek root "leptos" meaning thin, was subsequently
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Contact: Joseph Bonner
bonnerj@mail.rockefeller.edu
212-327-8998
Rockefeller University
11-Jul-2002


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