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Study: Muscles of obese programmed to collect fat
Scripps Howard News Service


October 11, 2005
Tuesday PM

In a new finding that may help explain why heavy people have so much trouble keeping weight off after they shed pounds, researchers report that muscles of the obese are genetically programmed to amass fat.

The scientists found that a particular fat-building enzyme is three times more abundant in the muscles of obese people than in the muscles of people who are lean, and that this propensity continued even when the cells were removed from the body and forced to grow in a lab.

"The cells of obese people remembered their metabolic program, which could help explain, in part, why losing weight and maintaining weight loss is so difficult," said Deborah Muoio, an assistant professor of medicine at Duke University and senior author of the study published Wednesday in the journal Cell Metabolism.

"The good news is it's possible to change your energy balance through exercise. Exercise can enhance muscle's ability to burn fat," she said.

The study is also important in addressing type 2 (insulin-resistant) diabetes.

An earlier study of the small group of female surgical patients that made up the research volunteers found that the obese individuals, while not diabetic, showed insulin resistance. The muscle of those individuals was laced with fat droplets, the researchers found, and showed 43 percent less capacity to burn fat than did the tissue of leaner subjects.

In the new research, the scientists did a comprehensive profile of gene activity in the tissue samples. They found that increased expression of the SCD1 fat-building enzyme by a particular gene not only had a link with obesity levels, but also corresponded with diminished fat-burning and changes in the fat composition of muscle.

But other genes known to make proteins keyed to fat production did not differ in activity between the obese and lean women in the study.

The researchers also investigated how muscle cells from the lean individuals behaved when forced to overproduce the SCD1 enzyme. And they found that under that circumstance, the otherwise lean cells mimicked the metabolism of obese cells, storing more fat and burning less fat as the amount of SCD1 was increased.

"Obesity is a very complex disease, and this metabolic pathway probably does not fully explain obesity, but we now know that SCD1 is at least a very important contributor," Muoio said.

Although the genetic call to store fat may be an inherited predisposition, Muoio suspects such genes are imprinted by some event earlier in life that changes gene activity, but not the underlying DNA sequence. This could be a chemical exposure or a deviation from good nutrition during a critical development period.

If that's the case, then the researchers conclude it may be possible to find drugs that could act to regulate the over-expression of SCD1 in cells as a prevention or treatment for obesity.


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