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Overproducing leptin receptors in fat cells may be key to halting weight gain

A new study by researchers at UT Southwestern Medical Center suggests that when fat cells increase in size as they do during the development of obesity the cells progressively lose receptors for the hormone leptin, a powerful stimulus for fat burning. Leptin, a hormone produced by the body's fat cells and involved in the regulation of body weight, was first discovered in 1994. It was thought leptin itself would be a key to curing obesity in humans, but the hypothesis did not readily translate into weight loss in obese people. Using mouse models, UT Southwestern researchers have now shown that if enough receptors are present on the fat cells, it is impossible for the cells to store fat and obesity would be blocked.

The new findings, appearing in an upcoming issue of the Proceedings of the National Academy of Sciences and currently available online, bring researchers a step closer to understanding obesity in humans, said Dr. Roger Unger, director of the Touchstone Diabetes Research Center at UT Southwestern and senior author of the study.

"We now think that people with naturally high levels of leptin receptors may not gain weight as rapidly over time as people who have low levels of leptin receptors," said Dr. Unger. "It could explain why some people can eat more and do not gain weight." To test this hypothesis, the UT Southwestern researchers used genetically modified rats in which the leptin receptor remained present in large quantities even during marked overfeeding. In normal mice, the high-fat diet caused massive obesity with enlargement of fat cells to almost three times their normal size. In mice with the forced overexpression of the leptin receptor on their fat cells no obesity occurred, even though they too were fed high-fat, highly caloric diets.

"The fat-storing function of the fat cells requires the disappearance of the leptin receptor," Dr. Unger said. "This is done in order to block the action of the leptin fat cells produce
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Contact: Katherine Morales
katherine.morales@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
1-Dec-2005


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