The study in mice shows that exercise causes muscle to release a peptide that builds the muscle's capacity for energy production and increases physical endurance, allowing for longer and more intense exercise.
The findings establish that the peptide, called musclin, is an "exercise factor," a hormone-like substance made by skeletal muscle in response to exercise and released into the bloodstream. The study shows that increased levels of circulating musclin trigger a signaling cascade that improves muscle performance and promotes production of mitochondria in muscle cells.
‘Musclin signaling promotes production of mitochondria in muscle cells and mitochondria are the cells' power plants. The study links the increase in mitochondria to improved aerobic capacity in the mice.’
"Exercise is an extremely powerful way to improve people's health, but unfortunately, increasing physical activity can be really difficult in many circumstances," says senior author Leonid Zingman, M.D., associate professor of internal medicine at the University of Iowa Carver College of Medicine and a physician scientist at the Iowa City Veterans Affairs Medical Center.
"We don't want to replace exercise by using this exercise factor, but if we can learn more about the mechanism, it might help us to increase exercise tolerance and make it easier for people to actually exercise. And if it is easier, people may exercise more."
The study was funded in part by grants from the Department of Veterans Affairs, the National Institutes of Health, and the Fraternal Order of Eagles Diabetes Research Center at the UI.
"The musclin infusion into the knockout mice was effective in rescuing the animal's exercise capacity in just one week," says first author Ekaterina Subbotina, Ph.D., a post-doctoral scholar in Zingman's laboratory.
The researchers also showed that infusing normal lab mice with musclin increased the animals' voluntary treadmill activity; the mice ran faster and longer on the treadmill than those that received a placebo infusion of saline.
Although the research focused primarily on the effect of exercise on musclin levels, even when mice were sedentary, those that lacked musclin had decreased levels of exercise endurance compared to sedentary mice in the control group, suggesting that musclin may promote muscle health, even during the low-level exercise of normal, everyday living.
The study was published online in the Proceedings of the National Academy of Sciences Early Edition