"Obesity is a very complex disease, and this metabolic pathway does not fully explain obesity, but it is a likely contributor," said Deborah Muoio, Ph.D., senior study author and assistant professor of medicine at Duke's Sarah W. Stedman Nutrition and Metabolism Center.
Excess fat storage in muscle tissue is a hallmark of obesity, and may contribute to problems such as diabetes and cardiovascular disease. The researchers discovered that skeletal muscle tissue and cells from obese people were programmed to store fat even when removed from the body and forced to grow in the laboratory. This finding suggests the gene is more active in obese people not only because of excess calorie intake, but also as a result of heritable changes in its regulation, Muoio said.
"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," Muoio said. "The good news is it's possible to change your energy balance through exercise. Exercise can enhance muscle's ability to burn fat," Muoio said. "This discovery also provides a potential drug target."
The results appear in the Oct. 12, 2005 issue of Cell Metabolism. The work was supported by National Institute of Diabetes & Digestive & Kidney Diseases, of the National Institutes of Health, the Pennington Biomedical Research Foundation and the American Diabetes Association.
Muoio suspects that the gene's behavior is altered in obese people because of epigenetic control alteration of gene activity states without variations in the DNA code. The
Contact: Becky Oskin
Duke University Medical Center