Imagine a future where you could unlock the fat-burning, energy-boosting benefits of a workout without ever lacing up your sneakers or breaking a sweat. For people grappling with obesity, metabolic disorders, or physical limitations that keep them from moving freely, that future just took a significant step closer. Scientists at Washington University School of Medicine have developed a groundbreaking compound called SLU-PP-332—and it’s showing remarkable promise in replicating the key metabolic perks of aerobic exercise, from torching more fat to reducing insulin resistance, especially for conditions like metabolic syndrome.
Let’s be clear: SLU-PP-332 isn’t a “magic pill” to replace the full value of physical activity (we’ll circle back to that). Instead, it’s a lab-engineered molecule that taps into the body’s natural energy-regulation system by activating a group of proteins known as estrogen-related receptors (ERRs).
ERRs are workhorses in high-energy organs—think the heart, liver, and skeletal muscles—where they control how the body uses energy, especially during physical activity. What makes SLU-PP-332 truly unique? Unlike other compounds, it activates
all three types of ERRs (α, β, and γ). Working in tandem, these receptors supercharge energy use, ramp up fat burning, and even boost muscle endurance—key effects of regular exercise.
The results from mouse studies speak for themselves:
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Mice treated with SLU-PP-332 developed more fatigue-resistant muscle fibers, letting them exercise for longer stretches without tiring out.
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They had far less fat buildup and used fatty acids for energy more efficiently—mirroring the metabolic shifts seen after weeks or months of consistent aerobic workouts.
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Their blood sugar control improved dramatically, a sign that their bodies were functioning more like those of healthy, active animals.
To grasp why SLU-PP-332 is a game-changer, let’s break down how muscles use energy. Your muscles naturally switch between two fuels: glucose (sugar) for short, intense bursts of activity, and fatty acids for long, low-intensity exercise (like a brisk walk).
Exercise rewires this balance: the longer you move, the more your muscles rely on fat for fuel. This shift also spurs your cells to build more mitochondria—the tiny “energy engines” that turn food into usable power. More mitochondria mean better endurance, smarter sugar processing, and less fat stored in the body.
SLU-PP-332 triggers exactly these same pathways. It encourages muscles to prioritize fat for energy, makes cells more energy-efficient, and supports overall metabolic health. This is especially critical for conditions like obesity and Type 2 diabetes, where the body struggles to break down fat effectively and muscles lose their ability to process energy properly.
In one key experiment, mice were fed a high-fat diet (to mimic obesity) and then treated with SLU-PP-332. The outcome?
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They gained significantly less weight compared to mice not given the compound.
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Their energy use at rest improved—meaning their bodies burned more calories even when inactive.
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They aced glucose tolerance tests, showing their bodies could process sugar as well as healthy, non-obese mice.
ERRs belong to the same protein family as estrogen receptors, but here’s the twist: they don’t bind to estrogen. Instead, they’re constantly active, acting as the “managers” of cellular energy. They control genes involved in fat burning, mitochondrial growth, and cell respiration—the processes that keep your metabolism running smoothly.
Scientists have studied ERRs for years, and the findings highlight just how vital they are:
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Mice missing ERRβ don’t survive past birth.
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Mice without ERRα or ERRγ develop serious health issues, including heart failure.
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On the flip side, mice with extra ERRγ in their muscles grow more “oxidative” muscle fibers (the kind that resist fatigue) and can exercise far longer than normal.
This makes ERRs a prime target for drugs that fight metabolic diseases—and SLU-PP-332 was built specifically to test if activating these receptors could replicate exercise’s benefits. Early tests confirm it works: SLU-PP-332 reaches high enough levels in both blood and muscle tissue to trigger these positive changes, and measurable amounts of the compound are still present in muscles 6 hours after injection in mice.
Dr. Bahaa Elgendy, a professor of anesthesiology at Washington University School of Medicine who led the research, is clear about the goal: “We can’t replace exercise; exercise is important on all levels… but there are many cases where a substitute is needed.”
That substitute could be life-altering for people who can’t exercise due to:
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Aging, which often leads to muscle loss and reduced mobility.
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Chronic illnesses like cancer, which can sap strength and limit activity.
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Genetic conditions that impair physical movement.
By mimicking the metabolic changes triggered by exercise, SLU-PP-332 could help these groups maintain muscle strength, avoid dangerous fat gain, and preserve metabolic health—even when staying active isn’t an option.
This research is still in its early stages, but the future is bright. The team has already developed next-generation versions of SLU-PP-332 that bind more tightly to ERRs and trigger even more significant changes in gene activity. In lab tests, these new compounds outperform the original—hinting that even more powerful “exercise mimics” are on the horizon.
Dr. Elgendy and his colleagues have partnered with Pelagos Pharmaceuticals, a biotech startup, to test these new compounds in animals with various diseases. Their plans include exploring how the drugs impact:
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Age-related decline (like muscle loss and reduced energy).
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Heart conditions, which often tie to poor metabolic health.
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Even brain health—early research suggests ERRs may play a role in fighting cognitive decline, though SLU-PP-332 itself doesn’t reach the brain (future ERR activators might).
The research is funded by the National Institute on Aging, part of the U.S. National Institutes of Health, with support from two awards: R21AG065657 and RF1AG077160.
SLU-PP-332 isn’t ready for store shelves yet—but it’s a huge leap forward in our understanding of how the body’s energy systems work. Exercise does more than burn calories: it shapes how our cells function, what fuels they prefer, and how strong our tissues are. Drugs that replicate these effects could offer new hope to the millions of people who need it most.
For now, exercise remains unmatched for overall health. But the day when “exercise in a pill” becomes a tool to support health—especially for those who can’t move—isn’t just a fantasy anymore. It’s getting closer.
Stay tuned: We’ll keep updating this site with the latest breakthroughs on SLU-PP-332 and similar compounds. And we want to hear from you—drop a comment below: Who do you think could benefit most from a compound like SLU-PP-332?
Whether you’re a healthcare provider, someone living with a metabolic condition, or just curious about the future of health tech, this is one story you won’t want to miss. Bookmark our page and check back soon for more updates!
