New drug boosts fat burning and increases muscle endurance without a workout

What if a pill could give your body some of the same benefits as a jog or bike ride? Researchers at Washington University School of Medicine have taken a big step in that direction with a compound called SLU-PP-332. Early studies in mice suggest this experimental drug could boost fat burning, improve blood sugar control, and increase muscle endurance—results usually tied to months of steady exercise.

No pill will ever replace the broad benefits of moving your body, but this new work shows it may be possible to capture some of exercise’s magic in people who can’t stay active because of illness, injury, or age.

SLU-PP-332 is designed to stimulate a group of proteins in your body known as estrogen-related receptors, or ERRs. These proteins act like internal switches that manage how your cells use energy. They are especially active in power-hungry organs such as the heart, liver, and skeletal muscles.

What makes this compound different is its ability to turn on all three types of ERRs—α, β, and γ—at once. Together, those proteins encourage cells to burn fat more efficiently, produce more energy, and resist fatigue. Mice treated with the drug developed more muscle fibers that don’t tire easily, giving them better stamina during exercise.

The impact didn’t stop at performance. Animals that received the compound showed less fat buildup, improved use of fatty acids, and steadier blood sugar levels. These shifts mirrored the kinds of internal changes seen after weeks of aerobic activity.

To see why SLU-PP-332 is so effective, it helps to look at how muscles normally power themselves. For quick bursts, muscles rely mostly on sugar, or glucose. But during longer, lower-intensity activities like walking or cycling, they gradually switch to burning fat. Over time, this process builds more mitochondria—the cell’s tiny power stations that turn food into energy. With more mitochondria, muscles can last longer, use sugar more efficiently, and store less fat.

SLU-PP-332 appears to flip many of those same switches without the workout. It boosts fat use inside muscles, increases their efficiency, and supports healthier metabolism overall. In mice fed high-fat diets, the compound reduced weight gain, helped their bodies burn more energy at rest, and made them handle sugar like healthier animals.

ERRs might sound like they’re tied to estrogen, but they don’t bind to the hormone itself. Instead, they’re constantly active and control a wide range of genes involved in fat burning, mitochondrial growth, and energy production.

Experiments over the years have shown just how vital they are. Mice missing ERRβ don’t survive to birth. Those lacking ERRα or ERRγ often suffer heart problems. On the other hand, mice with higher levels of ERRγ in their muscles develop more endurance-oriented fibers and can exercise longer. These discoveries made ERRs attractive targets for new treatments that could help fix broken energy systems in conditions such as obesity and heart disease.

SLU-PP-332 was built to test this idea directly, and early results confirm it can reach muscle tissue at levels high enough to make a difference, even hours after being given.

Bahaa Elgendy, a professor of anesthesiology at Washington University who leads the research, stresses that the team isn’t trying to make gym memberships obsolete. “We cannot replace exercise; exercise is important on all levels… But there are so many cases in which a substitute is needed,” Elgendy explained.

That substitute could be life-changing for people who can’t safely exercise. Older adults facing muscle loss, patients weakened by cancer, or those with genetic muscle conditions might all benefit from a drug that mimics training effects inside their cells.

And the research doesn’t stop with the first version of SLU-PP-332. Newer compounds created by the team bind even more tightly to ERRs, leading to stronger changes in gene activity. In lab tests, these updated molecules outperformed the original, hinting at a future with even more powerful exercise-mimicking medicines.

The medical potential is wide. For instance, other studies have found that turning on ERRα helps with fatty liver disease in mice. There’s also evidence that ERR activity may slow cognitive decline. SLU-PP-332 itself doesn’t cross into the brain, but future drugs could be designed to do so, possibly offering protection against neurodegenerative diseases such as Alzheimer’s.

The work is still in its earliest stages, but the momentum is clear. Elgendy and his colleagues, working with the biotech company Pelagos Pharmaceuticals, are preparing to test new versions of the compound in animal models of different diseases. They want to know how these drugs affect age-related muscle decline, heart health, and even brain function.

The research has been supported by the National Institute on Aging, part of the National Institutes of Health, through two separate awards. For now, scientists emphasize that nothing beats the wide-ranging benefits of actual physical activity, from improving mood to strengthening bones. Still, SLU-PP-332 and similar compounds represent a fresh way to help those who can’t rely on exercise alone.

It may not be a magic fitness pill just yet, but science is getting closer to building one. The day could come when maintaining health isn’t limited to lifting weights or jogging laps. Instead, medicine might be able to capture some of the same benefits in a bottle.

For decades, researchers have explored how exercise reshapes the body at a cellular level. Studies show that aerobic training increases mitochondria, improves insulin sensitivity, and helps muscles switch between burning sugar and fat. Animal research has also revealed the importance of ERR proteins.

When mice overproduce ERRγ in their muscles, they gain more oxidative fibers and develop superior endurance. Conversely, mice missing ERRα or ERRγ suffer from heart problems, underscoring the receptors’ role in energy regulation.

Other work has shown the potential for ERRs in treating disease. For example, activating ERRα in mice has been linked to improvements in fatty liver disease, a growing health problem worldwide. Research has also suggested ERRs may play a role in protecting brain cells, potentially delaying or reducing cognitive decline. These earlier findings set the stage for testing exercise mimetics like SLU-PP-332.

The findings could change the way doctors approach conditions tied to inactivity and metabolism. If future studies prove successful, people unable to exercise because of age, disability, or chronic illness might still gain some of the metabolic benefits of physical activity. That could mean better blood sugar control for those at risk of type 2 diabetes, reduced fat buildup for people struggling with obesity, or preserved muscle function in patients facing wasting diseases.

Beyond individual health, these drugs might also ease the burden of widespread conditions such as obesity and metabolic syndrome, which affect millions globally. A treatment that mimics exercise at the cellular level could help reduce healthcare costs and improve quality of life for large groups of people.

Research findings are available online in the journal ACS Publications.

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

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