An experimental drug touted as “exercise in a pill” has dramatically increased endurance in couch potato mice, even after a lifetime of inactivity. It appears to work by adjusting the body’s metabolism, allowing muscles to favor burning fat over sugar, researchers report in the May 2 Cell Metabolism.
Sedentary mice prodded into exercising ran for an average of about 160 minutes on an exercise wheel before reaching exhaustion. But mice given the drug for eight weeks could run for 270 minutes on average. These mice were burning fat like conditioned athletes, even though they had spent their whole lives taking it easy, molecular biologist Michael Downes and colleagues found.
Normally, running, cycling or other prolonged exercise eventually depletes available glucose in the blood, leaving the brain short of energy. The brain then sends an emergency stop signal. Athletes call this “hitting the wall.” Training and conditioning shift the body to burning fat for energy, leaving an ample supply of glucose for the brain and other organs.
Scientists at the Salk Institute for Biological Studies in La Jolla, Calif., developed the drug to activate a protein that regulates genes triggered during exercise. “We believe it’s tricked the body into thinking it’s done some training,” says Downes.
Called GW501516, the drug has been under study for more than a decade. Previous research had found that it could improve endurance, but only when combined with regular exercise (SN: 7/3/10, p. 18). The goal is not to boost athlete performance, though, but to help those who can’t exercise: people who are sick, disabled or elderly. It may also aid people who are obese or diabetic and do not have the stamina for even short-term exercise, Downes says.
“We know a lot about exercise, but we still don’t know how we obtain all the benefits,” says Rick Vega, a molecular and cellular biologist at Sanford Burnham Prebys Medical Discovery Institute in Orlando, who was not involved in the experiment. He praised the work as adding valuable information to the understanding of exercise and the drug in development. “The next step is really to show this has value in a medical application. To state the obvious, mice are not humans.”