Spiegelman, Jiandie Lin, PhD, the paper's first author, and their colleagues created transgenic mice that carried the PGC-1 gene in all their skeletal muscles. An added bit of DNA, called a promoter, caused the PGC-1 gene to now be active in Type II muscle fibers as well as Type I fibers.

When the scientists studied the bioengineered mice, they found that the muscles normally rich in Type II fibers now had a characteristically reddish color caused by the conversion of the fibers to oxygen-fueled Type I fibers. Futhermore, an endurance test showed that the muscles that had been treated with the PGC-1 genes contracted efficiently for seven minutes, while muscles from untreated mice worked efficiently only for about two minutes.

PGC-1 is naturally expressed, or active, in skeletal and heart muscle. The researchers found that PGC-1 is expressed at higher levels in muscles containing a lot of Type I fibers. When they looked at fibers that had been exposed to PGC-1, those fibers had more mitochondria and active genes normally in Type I fibers. Type I fibers use the mitochondria and oxygen as a source of energy as in aerobic exercise. In contrast, Type II, fast-twitch fibers get their energy mainly from the breakdown of sugar.

While the researchers caution they're not promising a new athletic stamina-enhancing drug, they say it's certainly possible that the might benefit people who are deficient in Type I muscle fibers because of medical conditions.

"Down the road, one would like to be able to incorporate it into some therapy where one has diseased muscles," said Rhonda Bassel-Duby, PhD, a molecular biologist at UT Southwestern and a collaborator on the paper. "One possibility is using [a drug] to give people on bed rest more endurance without having to do the exercise," she said.

Spiegelman, who is also a professor of cell biology at Harvard Medical School, adds that these findings in t
'"/>

Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
14-Aug-2002