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Mice lacking fat-making enzyme are leaner, more sensitive to leptin and insulin

A modern-day Rip van Winkle, just emerging from his long sleep, might notice a difference in todays Americans. The average American is much rounder, plumper, and heavier.

Obesity has been on the rise for the past two decades. The problem has now reached epidemic proportions, with more than 50 percent of the American population now classified as overweight or obese. While government-sponsored agencies try to spread the gospel of good eating and regular exercise, more and more Americans are finding that their clothes fit tighter every day. And no effective medical therapies currently exist for people with morbid obesity.

Whats the solution? Certainly not the miracle elixirs touted to melt away the pounds in a matter of weeks. The ultimate solution would be a way to stop the body from making fat. Sound like science fiction? Not to researchers at the Gladstone Institute of Cardiovascular Disease.

Theyve found a group of genes for an enzyme called DGAT (also called diacylglycerol acyltransferase). In animals, DGAT is essential for the last step in the production of triglycerides, the major component of fat. Mice that lack one of the DGAT enzymes, DGAT1, are leaner than mice with normal amounts of DGAT1and twice as activedespite their high-fat diets. Put simply, without DGAT1, the mice werent able to become obese.

Now the researchers have found a potential mechanism for this obesity resistance. They found that DGAT1-deficient mice are more sensitive to leptin, the hormone that tells the brain when the body has had enough to eat and encourages energy expenditure. They also found that these mice are more sensitive to insulin, and therefore potentially less likely to develop diabetes. The new findings are published in the April 15 issue of the Journal of Clinical Investigation.

This is good news. Obese and overweight people tend to develop type 2 diabetes, or insulin-resistant diabetes, because their cells become deaf to insulins
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Contact: Laura Lane
llane@gladstone.ucsf.edu
415-695-3833
University of California - San Francisco
10-Apr-2002


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