Researchers have identified a method for increasing endurance in mice by about 70 percent with the help of a drug that triggers the same genetic process as exercise.
If you’ve ever trained for an endurance sport, you’ve probably experienced the feeling of “hitting the wall.” Whether it’s running, swimming, or cycling, you get to a point where your brain wants to keep going, but your body just won’t cooperate.
Endurance training may not be the only way to avoid this phenomenon, according to a study published today in Cell Metabolism. Stimulating certain pathways in the body could also increase athletic endurance — with no training required.
A transcription factor in our genes known as PPAR delta (PPARD) increases endurance by activating pathways in the body when we train. “We discovered the critical function of PPARD in determining exercise-induced endurance enhancement,” said Michael Downes, one of the study authors and a staff scientist in the Gene Expression Laboratory at the Salk Institute for Biological Studies.
Our bodies begin to bonk when our brain is no longer getting enough glucose. Endurance training reprograms muscles to burn less glucose, preserving it for the brain. But the study showed that activating PPARD with a drug can have the same effect on endurance — with no need for training.
In their first round of trials, the researchers genetically removed PPARD from mice and ran them on a treadmill. They found that the genes normally activated by exercise were not induced, indicating that PPARD plays a very important role in exercise.
In the next trial, the mice were given a small-molecule drug, GW1516, to activate PPARD before they began exercising. Researchers observed that the drug increased fat oxidation in the muscles as well as stalled the effects of lost blood glucose on the brain. This resulted in the mice running much longer than before. Their time increased about 70 percent — from 160 minutes to 270 minutes — on the treadmill, despite having no previous endurance training.
“Although there’s no human trial,” Downes said, “the data we got from our mouse study highly suggest that the drug will translate into humans.”
This means that athletes would be able to increase their endurance much quicker than previously thought, while expending much less energy in the process.
The researchers recognize the possibility of professional athletes taking advantage of a drug like GW1516 as a performance enhancer, but they believe there is a much better use for their findings.
“PPARD agonists like GW1516 are currently listed on the WADA’s prohibited drug performance enhancing list,” Downes said. “We think this drug should never be used to gain a competitive advantage in any sport, but believe it has great potential to combat skeletal muscular diseases.”
PPARD was already known to have benefits for many health conditions and the results of this study confirmed that the potential is even greater than previously thought.
“It was never our intention to develop the drug as an endurance enhancer or a cure for ‘hitting the wall,’” Downes said. “The ultimate goal of this study was to understand how activation of PPARD in skeletal muscle contributes to health benefits, including protection against obesity, diabetes, muscle dystrophy, and fatty liver disease.”
Activating PPARD in people with these conditions could give them the benefits of increased endurance despite their mobility issues.