Exercise Gene

"When the animals were fed a high-fat diet and we studied their mitochondria, those mitochondria were not working efficiently," she says, and when mitochondria aren't burning fat properly the muscles can't function as well. "There are many roadways in the mitochondria that ultimately allow them to burn fat. What we observed was somewhat of a traffic jam."

In the skeletal muscle, the mitochondria take fuel, in this case carbohydrates and fats from the food we eat. The food is then converted by the mitochondria into another kind of fuel that allows muscle movement.

"When the mitochondria are fed fat, they attempt to adapt so that they can utilize fats effectively," Muoio says. "The problem is, if you think of it as a merging highway, certain parts of the highway adapt so there's quite accelerated fat burning. But the other parts are not adapting, and so what occurs is somewhat of a bottleneck. As a result, fats are what we call 'incompletely burned.'" She thinks that the presence of these incompletely burned intermediates may be what triggers insulin-resistance in the rats, an early sign of diabetes.

"Obesity and diabetes go hand in hand… under conditions of a high fat supply to the muscle, the tissue becomes insulin-resistant, not responding to insulin properly," Muoio explains. "If insulin isn't working properly then blood sugar can rise to what is considered dangerously hi levels, and this causes damage in a lot of different tissues."

But, as the researchers reported in the Journal of Biological Chemistry, when half of the rats were exercised for two weeks, while continuing to eat the diet, their blood sugar levels returned to normal, insulin sensitivity went back to normal, and at the same time there was an improvement in mitochondrial function.

The exercise was found to have activated a gene called PGC1-alpha. The gene, which regulates how the mitochondria of muscle cells metabolize fuel — how well muscles burn energy. When the gene is activated it tells muscle cells to burn fat more efficiently, so the rat's muscles stayed healthy, even as they continued their fatty diet.

"PGC1 is directing the crew that, builds the mitochondria and the roadways, to handle excess fat," Muoio explains. "For someone active… their mitochondria are better at coping with an extra fat load, and that type of diet isn't as detrimental."

She found that without exercise, the obese rats on the high-fat diet showed less activity in the gene. Muoio says, "The exercise actually prevented the diet-induced decline in PGC1, so when the animals were on a high-fat diet and they were exercising, their PGC1 levels stayed high."

This material is made possible by the the Journal of Biological Chemistry and the American Society for Biochemistry and Molecular Biology.

And as the researchers say this isn't the only gene that gets activated by exercise, it's unlikely that a drug could ever replace a good workout.
"It's unlikely that activating this one player is going to mimic the entire response of getting exercise… in reality, I don't think that scientists or pharmaceutical companies will ever develop a drug that can substitute for exercise," she says.