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Muscle of obese 'programmed' to amass fat, genetic study finds

The skeletal muscle of severely obese people is "programmed" to amass fat, a study in the October 2005 issue of Cell Metabolism reveals. The findings suggest that muscle bears a metabolic memory of obesity, which may help to explain why sustained weight loss can be difficult despite cutting calories, according to the researchers. Exercise might more successfully override the aberrant metabolic program in muscle, they suggest, thereby improving the long-term prognosis of those prone to obesity.

A diverse team of researchers found that the fat-building enzyme stearoyl-CoA desaturase-1 (SCD-1) is three times more abundant in muscle taken from obese people than in muscle from those who are lean. The newly discovered elevation in enzyme activity elucidates an important link between obesity, diabetes, and abnormal fat buildup in muscle, said study author Deborah Muoio of the Sarah W. Stedman Nutrition and Metabolism Center at Duke University Medical Center.

"Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and the accumulation of fat droplets in muscle, but the underlying causes of these perturbations have been unknown," Muoio said. "We've now shown that SCD1 is at least a very important contributor to changes in lipid handling within muscle and the progression of obesity."

The researchers examined muscle removed from lean and obese patients during surgery. An earlier study had found that the obese individuals, while not diabetic, did show severe insulin resistance. The muscle of those individuals was laced with fat droplets, they found, and also showed a 43% decline in the ability to burn fat.

Results of a comprehensive profile of gene activity showed a link between obesity and a 3-fold increase in muscle SCD1 levels. That increase in enzyme expression and activity also corresponded with diminished fat burning and changes in the fat composition of muscle. In contrast, many other genes with known roles in f
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Contact: Heidi Hardman
hhardman@cell.com
617-397-2879
Cell Press
11-Oct-2005


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