New drug mimics health effects of exercise, say researchers

Scientists have managed to mimic the health effects of exercise in mice, simply by using a pill, according to a study published in Cell Metabolism.

The drug activated a genetic pathway that is triggered by running, which led mice to burn off more fat and increase their stamina levels, despite them being sedentary.

The researchers say this could mean that, for people who are unable to exercise due to illness or disability, the benefits of fitness training could be achieved pharmacologically instead.

“It means you can improve endurance to the equivalent level as someone in training, without all of the physical effort," says lead author Weiwei Fan from Salk Institute, California in the U.S.

The drug, known of as GW501516 (GW), activates a gene called PPAR delta (PPARD), which has previously been associated with improved weight control and insulin responsiveness in mice.

For the current study, high doses of GW were given to sedentary mice over an eight-week period.  The animals were then subjected to treadmill tests to see how long they could run for and the results were compared with those for sedentary mice that had not been given the drug.

Fan and colleagues found that the control mice could run for about 160 minutes before they became exhausted. The experimental mice, on the other hand, could run for about 270 minutes –which is approximately 70% longer.

In both groups, mice became exhausted once their blood sugar level fell to around 70 mg/dL, suggesting that exhaustion was the result of a low blood sugar level (hypoglycemia).

Further tests revealed that the drug had altered the expression of 975 genes. Genes involved in fat breakdown became more active, but surprisingly, genes involved in the breakdown of sugar for energy were suppressed.

Fan and team concluded that the PPARD pathway stops sugar from being used as an energy source during exercise, possibly as a means of preserving brain function. Although muscle tissue can burn either fat or sugar, the brain uses sugar, which explains why athletes experience both physical and mental exhaustion once their glucose supplies have run out.

According to the authors, the drug basically causes the body to burn fat more quickly, but sugar more slowly. When mice are given the drug, the drop in blood sugar that causes exhaustion therefore occurs later than it usually would.

Co-author Michael Downes says: "This study suggests that burning fat is less a driver of endurance than a compensatory mechanism to conserve glucose… PPARD 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."

Pharmaceutical companies are now interested in developing clinical trials to test the drug in humans. Fan and team hope that therapeutic uses could range from increased fat burning among overweight and obese people, to improved fitness levels among patients due to undergo surgery.


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