ROANOKE TIMES
Copyright (c) 1996, Roanoke Times
DATE: Thursday, August 15, 1996 TAG: 9608150051
SECTION: NATIONAL/INTERNATIONAL PAGE: A-9 EDITION: METRO
SOURCE: Associated Press
Surprisingly skinny mice created in a Seattle genetics lab may offer hints at why some people can eat all they want and still stay thin.
Researchers have found that with a single genetic alteration, they can turn up a natural metabolic furnace in mice so the animals burn more fat. Experts said that people eventually might be able to control their weight by doing the same thing, or by exploiting related processes.
Mice with the mutation have about 6 percent body fat, compared with about 15 percent in their unaltered brethren. But even more impressive, the genetically altered mice can eat a high-fat diet without ill effects.
Even after four months on a diet with the fat content of a Sausage McMuffin, mice with the mutation had bulked up to only the normal mouse body fat content.
``That's what is the most dramatic,'' said pharmacologist G. Stanley McKnight of the University of Washington in Seattle. ``When you put these animals on a diet that's more like what Americans typically eat, they still stay thin.''
Scientists will have to learn much more about what's going on in the thin mice before drugs can be developed for humans. And because the field of obesity research is full of mutated mice, the best drugs may well come from another line of research.
``These kinds of experiments ultimately will produce a great deal of insight about how people regulate their body fat content,'' said Dr. Bradford Lowell, an endocrinologist at Beth Israel Hospital in Boston.
The University of Washington researchers produced the skinny mice by deleting a single gene in the animals. That deletion altered the properties of an enzyme, known as protein kinase A, in the brown fat of the animals.
``Basically there are two kinds of fat, and white fat is the kind of storage depot that we all know and love,'' McKnight said. ``Brown fat is a much more metabolically active and more specialized tissue.''
Brown fat appears to be involved in regulating body heat. Rather than serving as a passive energy repository, it responds to cold by burning other sources of energy, including white fat. Past studies have found that brown fat is more abundant in hibernating animals, newborn infants and maybe even adults who have spent lots of time outdoors in wintry climes.
The part of the enzyme that the Seattle researchers altered regulates the process that brown fat uses to turn energy into heat. Changing the structure of the enzyme accelerates that process, making it consume more energy, the Seattle researchers reported in today's issue of the journal Nature.
That finding might help explain why some people who maintain sensible diets are overweight while others can eat recklessly and stay thin.
But it won't explain everything. Researchers estimate that dozens of genes governing a number of processes are involved in controlling body fat.
A drug that had the same effect in humans as the genetic alteration does in mice conceivably could help humans control their weight. But such a drug probably won't be necessary, Lowell said, because an earlier step in the fat-burning pathway has already shown more promise as an intervention point.
``It's an incremental advance in the field,'' Lowell said of the Seattle research. ``There will be further refinements of these types of experiments.''
LENGTH: Medium: 66 lines ILLUSTRATION: GRAPHIC: Chart by AP: The lean gene. KEYWORDS: MGRby CNB