"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."While she says further studies need to be done to prove a direct link, it does give couch potatoes even more reason to pop a sweat. "Human muscle also expresses pgc1 alpha, and the human pgc1 responds similarly to environmental challenges, so it's increased by exercise training and decreased by a hi fat diet," Muoio explains. Adding that, "People who are very active can afford to eat more fat and more calories in general and that's because they're burning the extra energy. In the instance of someone who sits around on the couch and they eat extra food, those calories are stored as fat and that fat causes havoc."
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.
Muoio's research was published in the Journal of Biological Chemistry in September 30, 2005 (280: 33588 - 33598), and was funded by the American Diabetes Association, GlaxoSmithKline, and the National Institutes of Health.