‘Exercise in a bottle’ drug helps the body burn more fat, use energy more efficiently

A new drug may one day help fight obesity and related diseases by mimicking the benefits of aerobic exercise—without the need to move a muscle. Scientists at Washington University School of Medicine have developed a compound called SLU-PP-332 that shows strong promise in helping the body burn more fat, use energy more efficiently, and reduce insulin resistance, especially in conditions like metabolic syndrome.

While no pill can replace the full value of physical activity, new research suggests that certain molecules can copy key changes exercise brings about inside your muscles. These discoveries may open the door to powerful new treatments for people who can’t exercise because of age, injury, or chronic illness.

SLU-PP-332 is a lab-made compound that activates a group of proteins called estrogen-related receptors, or ERRs. These proteins help control how your body uses energy during physical activity. They’re most active in high-energy organs like the heart, liver, and skeletal muscles.

What makes SLU-PP-332 special is that it activates all three types of ERRs—α, β, and γ—which together help boost the body's energy use, fat burning, and muscle endurance. In studies using mice, this drug increased the type of muscle fibers that are most resistant to fatigue. That means animals on the drug could exercise longer without getting tired.

But the benefits weren’t limited to performance. Mice given SLU-PP-332 showed lower fat buildup, better use of fatty acids for energy, and improved blood sugar control. These changes are hallmarks of what the body normally experiences after weeks or months of regular aerobic exercise.

To understand why SLU-PP-332 works so well, it helps to know how skeletal muscle uses energy. Depending on the situation, your muscles can switch between using sugar (glucose) and fat (fatty acids) as fuel. Short bursts of activity rely on sugar, while long, low-intensity movement tends to use fat.

Exercise shifts this balance. The longer you move, the more your muscles rely on fat. This switch also encourages your cells to build more mitochondria—the tiny engines that convert food into energy. More mitochondria mean more endurance, better sugar use, and less fat storage.

SLU-PP-332 triggers many of the same pathways. It boosts fat use in muscles, helps them become more efficient, and supports overall metabolic health. These effects are especially important in diseases like obesity and type 2 diabetes, which involve poor fat breakdown and reduced muscle energy capacity.

Mice fed a high-fat diet and then treated with SLU-PP-332 showed less weight gain, improved energy use while resting, and better results on glucose tolerance tests. That means their bodies processed sugar more like healthy, fit animals.

ERRs belong to the same family as estrogen receptors but don't bind to estrogen itself. Instead, they’re active all the time and are key players in how cells manage energy. They help control genes involved in fat burning, mitochondrial growth, and cellular respiration.

Over the years, scientists have tested mice with changes in ERR function. Mice missing ERRβ die before birth. Those without ERRα or ERRγ develop problems like heart failure. On the flip side, mice that overexpress ERRγ in their muscles grow more oxidative muscle fibers and can exercise for longer periods. This makes ERRs attractive drug targets for diseases that involve energy failure, like obesity and heart disease.

Researchers have long suspected that activating these receptors with drugs could mimic some of the changes brought on by aerobic exercise. SLU-PP-332 was built to test that idea.

In earlier tests, it showed up in both blood and muscle tissue at levels high enough to cause these effects. Even six hours after being injected into mice, the drug was still found at measurable concentrations in muscle.

Bahaa Elgendy, a professor of anesthesiology at Washington University School of Medicine in St. Louis, leads the research. Elgendy shared that the goal isn’t to replace exercise. “We cannot replace exercise; exercise is important on all levels… But there are so many cases in which a substitute is needed,” he said.

For people with muscle wasting due to aging, cancer, or genetic disorders, exercise might not be possible. That’s where a drug like SLU-PP-332 could be a game-changer. By simulating the metabolic changes triggered by physical activity, it may help maintain strength and health in people who can't stay active.

Newer versions of SLU-PP-332 have also been developed. These next-gen compounds bind more strongly to ERRs and lead to even greater changes in gene activity. In lab tests, they outperformed the original version of the drug, suggesting that even more powerful exercise mimetics could be just around the corner.

These compounds may have wide medical use. For example, other studies have shown that ERRα activation helps improve fatty liver disease in mice. There's even evidence that ERRs play a role in fighting cognitive decline. Although SLU-PP-332 doesn’t cross into the brain, other ERR-activating drugs might be able to protect neurons and slow conditions like Alzheimer’s disease.

The work is still in its early stages, but the team has big plans. Elgendy and colleagues, in partnership with a biotech startup called Pelagos Pharmaceuticals, are preparing to test new compounds in animals with various diseases.

They want to explore how these drugs affect aging-related decline, heart problems, and possibly brain health. If successful, this could change how medicine treats conditions tied to metabolism and inactivity.

Funding for the research came from the National Institute on Aging, part of the U.S. National Institutes of Health. Two awards—R21AG065657 and RF1AG077160—supported the work.

The science behind SLU-PP-332 shows how deep our understanding of the body’s energy systems has become. Instead of simply burning calories, exercise shapes how your cells work, what fuels they prefer, and how strong your tissues can be. Drugs that copy these effects could give new hope to those who need help most.

Even if a magic fitness pill isn't ready for the market yet, scientists are getting closer to building one. For now, physical activity remains unmatched in its power—but a future where movement is just one of many tools to protect your health is quickly coming into view.

Note: The article above provided above by The Brighter Side of News.

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