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doreen T
Thu, Oct-04-01, 11:34
By Amy Norton

NEW YORK, Oct 04 (Reuters Health) - By inactivating a metabolism-related gene, scientists have created a leaner, meaner mouse that can eat as much as its flabbier brethren. Knocking out the gene, researchers found, allowed some of the animals' fat stores to be converted to a more weight-friendly type of fat that promotes calorie-burning.

They say their finding could offer a new target for fighting obesity in humans.

Prior to these experiments, no one knew that the gene--which encodes a protein called 4E-BP1--was even involved in metabolism, the study's lead author told Reuters Health.

"This is very surprising," said Dr. Nahum Sonenberg of McGill University in Montreal, Canada.

He and his colleagues discovered the role of 4E-BP1 in metabolism and body fat by comparing a group of mice that lacked the gene for 4E-BP1 with normal animals.

The investigators found that this genetic tinkering allowed some of the animals' white fat--the type that stores energy and expands to make jeans too tight--into brown fat, the type that burns calories to produce heat and keep the body warm on cold nights.

Human adults have very little brown fat, Sonenberg explained. But, he said, there has been a good deal of interest in finding a way to transform some of the padding around our middles into the more-efficient brown fat.

In the mice his team studied, such a fat conversion did occur, and it resulted in mice that burned more calories and carried less body fat. Mice lacking the 4E-BP1 gene weighed about 10% less than normal mice, despite eating just as much food. Instead, the weight difference was due to a sharp reduction in the animals' white fat and a revved up metabolism, according to the report in the October issue of Nature Medicine.

According to Sonenberg and his colleagues, "this study raises the intriguing possibility that inactivation of 4E-BP1 could be explored as a treatment for obesity."

In principle, Sonenberg said, the white-to-brown fat conversion seen in these mice could happen in humans as well.

However, he stressed, there will be no magic pill in the near future.

In an editorial accompanying the report, California researchers note that the study "provides more clues for solving the mysteries of obesity."

They also point out, however, that a host of obesity-related genes--ranging from those involved in food intake to those that regulate fat development--have been uncovered in mouse studies. These genes share similarities, but how they all fit together in the complex metabolic system remains unclear, according to Drs. Hubert C. Chen and Robert V. Farese Jr. of the University of California, San Francisco.

The new finding "expands the list of genes" involved in this system, the editorialists write.

SOURCE: Nature Medicine 2001;7:1102-1103, 1128-1132.