It's well known that the way to increase fitness and endurance is through training, but what if the same effects could be achieved with a drug, a kind of "workout pill?" Scientists at the Salk Institute found that when they fed sedentary mice a certain chemical compound, they could run seventy percent longer. If a similar treatment works in humans, it could open doors for fitness training for athletes, the elderly, obese or otherwise mobility-limited.

The researchers expanded upon earlier work around a specific genetic pathway that is triggered by running. They identified a chemical compound that activates the same gene, bestowing a resistance to weight gain and responsiveness to insulin that is seen in long-distance runners.

The team gave a group of sedentary mice a higher dose of the compound for a longer period of time than in previous experiments and found they could run 270 minutes before becoming exhausted, compared to just 160 minutes for a control group of sedentary mice that did not receive the drug.

"A hundred minutes is a huge increase in performance for sedentary mice that never actually trained; that's gigantic." says the Salk Institute's Ronald Evans. "It would take a lot of diligent training every single day to get that benefit and these mice are getting it just because we're feeding them a drug that is re-programming their metabolic properties."

We recently saw different research in which a pill was able to confer different benefits of exercise without the physical training, namely enhancing muscle mass.

The Salk team examined what was happening to cause the endurance boost in the mice given the drug and found genes that manage burning fat increased while those that help burn carbohydrates for energy were suppressed. The scientists believe that directing the body to burn fat as an energy source for the muscles may be the genes' way of preserving sugar for the brain.

"This study suggests that burning fat is less a driver of endurance than a compensatory mechanism to conserve glucose," says Salk senior scientist Michael Downes, a co–senior author of the paper. "(The gene activated by the drug) is suppressing all the points that are involved in sugar metabolism in the muscle so glucose can be redirected to the brain, thereby preserving brain function."

The Salt Institute research team (from left): Wanda Waizenegger, Weiwei Fan, Ryan Lin, Ronald Evans, Ruth Yu and Mingxiao He(Credit: Salt Institute)

A pill that delivers some of the benefits of exercise without the physical effort could be prescribed one day to help people with obesity or type-2 diabetes burn fat, among other potential applications.

"If you're in a wheelchair; if you're a soldier who was injured; if you're in the hospital getting surgery, you're immobilized in all these cases," says Evans. "If you can bring a small molecule into the picture that can confer the benefits of fitness without training, you can really help a lot of people."

The study appears in the most recent issue of the journal Cell Metabolism.

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