By LEE BOWMAN
Scripps Howard News Service
May 10, 2005
Based on an experiment with mice, researchers at the Washington University School of Medicine in St. Louis concluded that normal metabolism requires what they term "new" fat, as opposed to fat stored in cells. They say their work offers further evidence that a healthy diet should include an adequate source of fat.
"These findings underscore the importance of a balanced diet for healthy metabolism and weight loss," said Dr. Clay Semenkovich, a professor of medicine and cell biology and senior author of the study appearing in the May issue of the journal Cell Metabolism.
New dietary guidelines issued by the government this year emphasize the need to include some fats, in the form of healthy oils, as well as smaller portions of "solid fats" in discretionary foods, like butter.
Semenkovich noted that fats taken in directly from foods or generated from sugars spark a cascade of gene activity in the liver that's necessary to maintain healthy blood levels of sugar, cholesterol and other fats. Old-fat stores alone failed to put those metabolic pathways into action, the researchers found.
"The study supports the notion that the source of fats affects their physiology," Semenkovich said. "New fats are required to burn fat normally and to maintain glucose and cholesterol levels within the normal range."
For the experiment, the scientists inactivated fatty-acid synthase, an enzyme that generates new fat from carbohydrates, in the livers of mice. They then fed those mice a diet completely lacking in fat, and the animals developed low blood sugar and fatty livers.
"It's quite paradoxical," Semenkovich said. "When we inactivated fatty-acid synthase in the liver and eliminated fat in the diet, the animals became sick, with livers full of fat."
Further study showed that in the absence of new fat, the mice exhibited a marked decline in the activity of genes critical for the metabolism of glucose, fatty acids and cholesterol. Those genes, in turn, are controlled by an energy-management gene, called PPARa, that is known to be activated by fatty acids.
The health of the test mice was restored when the researchers put fat back into their diets.
"In short, all fatty acids are not created equal, at least in the liver," Semenkovich said.
More study is needed to understand the mechanism by which nutrient sensors in the body distinguish between different sources of fat, fresh or stored, the researchers said.
If these triggers can be identified, Semenkovich said, it might eventually be possible to use specially engineered fats to boost healthy liver metabolism and help treat chronic diseases such as obesity, diabetes and heart disease.
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