Could a drug offer the benefits of exercise?

The drug belongs to a class known as "exercise mimetics," which provide some of the benefits of exercise without increasing physical activity. (Credit: Getty Images)

New research with mice shows promising results that could lead to the development of a weight-loss drug that mimics exercise.

As reported in the Journal of Pharmacology and Experimental Therapeutics, the compound led obese mice to lose weight by convincing the body’s muscles that they are exercising more than they really are, boosting metabolism. It also increased endurance, helping mice run nearly 50% further than they could before. All without the mice lifting a paw.

The drug belongs to a class known as “exercise mimetics,” which provide some of the benefits of exercise without increasing physical activity. The new treatment, currently in the early stages of development, could one day be tested in people to treat diseases like obesity, diabetes, and age-related muscle loss.

The research comes as drugs like Ozempic have provided a breakthrough in reducing appetite, helping treat these metabolic diseases.

But the new drug, SLU-PP-332, doesn’t affect appetite or food intake. Nor does it cause mice to exercise more. Instead, the drug boosts a natural metabolic pathway that typically responds to exercise.

In effect, the drug makes the body act like it is training for a marathon, leading to increased energy expenditure and faster metabolism of fat in the body.

“This compound is basically telling skeletal muscle to make the same changes you see during endurance training,” says lead author Thomas Burris, a professor of pharmacy at the University of Florida.

“When you treat mice with the drug, you can see that their whole body metabolism turns to using fatty acids, which is very similar to what people use when they are fasting or exercising,” Burris says. “And the animals start losing weight.”

The new drug targets a group of proteins in the body known as ERRs, which are responsible for activating some of the most important metabolic pathways in energy-gobbling tissues like muscles, the heart, and the brain. The ERRs are more active when people exercise, but they have proven difficult to activate with drugs.

In another paper published in March, the researchers reported that they had successfully designed SLU-PP-332 to boost activity of the ERRs. They also observed that the compound allowed normal-weight mice to run for 70% longer and 45% further than mice not receiving the drug.

In the new research, the team tested the drug on obese mice. Treating obese mice twice a day for a month caused them to gain 10 times less fat than untreated mice and lose 12% of their body weight. Yet the mice kept eating the same amount of food and didn’t exercise any more.

“They use more energy just living,” Burris says.

So far, the drug hasn’t generated any severe side effects. The next step in developing SLU-PP-332 into a drug candidate will be to refine its structure, ideally making it available as a pill instead of an injection. Then the drug would be tested for side effects in more animal models before making the jump to human trials.

The greatest hope for the new drug might be in maintaining muscle mass during weight loss—which often threatens lean muscle mass—or during aging, when the body naturally responds less strongly to exercise. But it will take more research to understand the drug’s full potential.

“This may be able to keep people healthier as they age,” Burris says.

Additional coauthors are from Washington University in St. Louis and St. Louis University.

Source: University of Florida