People with diabetes see whitening of the mix of muscle.
"For a long time, the red-to-white shift was thought to make muscle less responsive to insulin, a hormone that lowers blood sugar," Lin said. "But this idea is far from proven. You lose red muscle when you age or develop diabetes, but is that really the culprit?"
To find out, the team set out to find a protein that drives the formation of white muscle. They sifted through microarray data sets from public databases and identified a list of candidate proteins that were prevalent in white muscle but not in red.
Further studies led the team to focus on a protein called BAF60c, a sort of "zip code" mechanism that tells the cells when and how to express certain genes. The Lin team made a transgenic mouse model to increase BAF60c only in the skeletal muscle. One of the first things they noticed was that mice with more BAF60c had muscles that looked paler.
"That was a good hint that we were going in the white-muscle direction," said lead author Zhuo-xian Meng, a research fellow in Lin's lab.
They used electron microscopy to see the abundance of mitochondria within the muscle, and confirmed that muscle from BAF60c transgenic mice had less mitochondria than the normal controls.
"We saw predicted changes in molecular markers, but the ultimate test would be seeing how the mouse could run," Lin said.
If the BAF60c mice could run powerfully for short distances but tired quickly, the scientists would be able to confirm that the BAF60c pathway was a key part of the creation of white muscle.
Using mouse treadmills, they compared the endurance of BAF60c mice to a control group of normal mice, and found that the BAF60c transgenic mice could only run about 60 percent of the time that the control group could before tiring.
"White muscle uses glycogen, and the
|Contact: Laura J. Williams|
University of Michigan