SLU-PP-332: The Oral Peptide That Mimics Exercise and Boosts Mitochondrial Health

Modern research into metabolic dysfunction and mitochondrial health has opened the door to a new class of therapies: exercise mimetics. Among these, one molecule stands out—SLU-PP-332. This orally active peptide acts as a potent estrogen-related receptor alpha (ERRα) agonist, mimicking the cellular and physiological effects of aerobic exercise, without requiring intense physical exertion.

In this in-depth article, we explore the mechanism, benefits, ideal users, safety, and therapeutic potential of SLU-PP-332. We’ll also examine the scientific research backing its use for fat loss, glucose control, aging, endurance, mitochondrial rejuvenation, and more.

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What Is SLU-PP-332?

SLU-PP-332 is a synthetic small molecule and oral peptide designed to selectively activate estrogen-related receptors (ERRs)—especially ERRα, a key regulator of energy metabolism and mitochondrial biogenesis. It belongs to a class of compounds known as exercise mimetics because it reproduces many of the metabolic and structural effects of physical activity at the cellular level.

Unlike injectables or performance-enhancing drugs, SLU-PP-332 is taken orally and does not require cycling. It’s well-tolerated, non-hormonal, and does not suppress endogenous production of any key hormone or peptide.

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Mechanism of Action: Activating ERRα to Mimic Exercise

What Is ERRα?

Estrogen-related receptor alpha (ERRα) is a nuclear receptor—not directly involved in estrogen signaling—that plays a critical role in regulating:

• Mitochondrial biogenesis

• Fatty acid oxidation

• Glucose metabolism

• Oxidative phosphorylation

• Thermogenesis and cellular respiration

It is highly expressed in energy-demanding tissues like skeletal muscle, heart, and brown fat. When activated, ERRα turns on genes that support energy expenditure, fat metabolism, and cellular repair—functions that are naturally boosted during endurance exercise.

How SLU-PP-332 Works

SLU-PP-332 binds to and activates ERRα with high affinity, triggering the expression of hundreds of exercise-related genes. These include:

• PGC-1α: Master regulator of mitochondrial biogenesis

• GLUT4: Glucose transporter upregulated by insulin and exercise

• UCPs (uncoupling proteins): Enhance thermogenesis and energy expenditure

• Fatty acid oxidation enzymes: Boost lipid metabolism

The result is a broad shift in cellular energy metabolism—from storage to usage—much like what happens during aerobic training.

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Proven Benefits of SLU-PP-332

1. Mimics the Effects of Aerobic Exercise

SLU-PP-332 has been shown to reproduce many of the cellular and physiological changes seen in physically trained animals. In mouse studies, SLU-PP-332 led to:

• Increased running endurance

• Improved VO₂ max

• Enhanced capillary density in muscle

• Shift toward oxidative muscle fibers

• Higher mitochondrial content

It essentially transforms “sedentary” muscles into metabolically active, endurance-ready tissue—even without physical training.

2. Supports Fat Loss and Metabolic Health

In models of diet-induced obesity, SLU-PP-332 produced:

• Reduction in white adipose tissue (WAT)

• Lower fasting insulin and glucose

• Improved glucose tolerance

• Reversal of hepatic steatosis

• Reduced inflammation in liver and adipose tissue

This suggests it can be highly effective for those struggling with:

• Insulin resistance

• Fatty liver (NAFLD/NASH)

• Obesity

• PCOS and metabolic syndrome

3. Restores Mitochondrial Function

Mitochondrial dysfunction is at the root of many chronic diseases and the aging process. SLU-PP-332 has demonstrated the ability to:

• Increase mitochondrial density

• Restore oxidative phosphorylation efficiency

• Enhance ATP production

• Reduce mitochondrial DNA damage

• Upregulate mitophagy (removal of damaged mitochondria)

This makes SLU-PP-332 especially valuable in aging populations or anyone with chronic fatigue, fibromyalgia, or neurodegenerative risk.

4. Cardioprotective Properties

In preclinical heart failure and ischemia-reperfusion models, SLU-PP-332 has shown:

• Improved cardiac contractility

• Lower cardiomyocyte apoptosis

• Enhanced fatty acid oxidation in cardiac tissue

• Reduced pathologic remodeling and fibrosis

These findings suggest potential future use in:

• Heart failure with preserved or reduced ejection fraction (HFpEF / HFrEF)

• Cardiac ischemia recovery

• Post-infarct metabolic support

5. Anti-Aging and Inflammation Reduction

SLU-PP-332 suppresses age-associated inflammatory markers like:

• IL-6

• TNF-α

• CRP

It also supports autophagy, mitophagy, and fibrosis attenuation in organs like the liver, heart, and kidney—critical factors in aging.

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Clinical Research: What Do the Studies Show?

Several preclinical studies have highlighted the wide-ranging impact of SLU-PP-332:

Billon et al. (2023)

SLU-PP-332 induced an ERRα-dependent exercise gene signature in sedentary mice, leading to improved endurance, capillary density, and mitochondrial markers.

Xu et al. (2023)

SLU-PP-332 and other ERR agonists improved cardiac metabolism, restored mitochondrial function, and reversed heart failure pathology.

Wang et al. (2023)

ERR agonism with SLU-PP-332 reversed inflammation and mitochondrial damage in aging kidney tissue, showing anti-fibrotic and rejuvenating effects.

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Who Should Consider SLU-PP-332?

This peptide has broad applications for anyone with impaired metabolic function, low energy, or age-related decline. It may be ideal for:

Sedentary Individuals or Seniors

• Those unable to exercise due to injury, arthritis, or disability

• Aging adults with mitochondrial decline and loss of endurance

Metabolic Syndrome, PCOS, and Insulin Resistance

• Elevated glucose, insulin, or HOMA-IR

• Abdominal obesity

• NAFLD/NASH

• Hormonal imbalances tied to metabolic dysfunction

Athletes or Weekend Warriors

• Seeking improved mitochondrial capacity

• Enhanced endurance and fat oxidation

• Recovery support without increasing training volume

Biohackers and Longevity Seekers

• Interested in NAD+ enhancement, mitochondrial repair, and autophagy

• Preventive anti-aging strategies

• Complement to exercise and caloric restriction mimetics

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Dosing and Duration

Oral Delivery

SLU-PP-332 is taken orally, making it extremely convenient compared to injectable peptides.

No Need to Cycle

Unlike many peptides that must be cycled to prevent desensitization, SLU-PP-332 can be taken continuously. Its mechanism works via gene transcription and receptor activation, not pituitary feedback loops or hormonal axes.

Suggested Dosing

Most preclinical modeling supports a daily dose for ongoing benefits. Human doses are still being studied, but based on current clinical trends:

• Starting dose: 0.25mg 1 to 3 times daily

• Advanced use: Up to 1.5mg 3 times daily daily depending on body size and response

Always consult a knowledgeable provider before starting any investigational or research peptide.

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Safety and Side Effects

No Known Toxicity

• SLU-PP-332 has no reported liver, kidney, or cardiac toxicity in preclinical trials.

• It does not suppress hormones, stimulate appetite, or act as a stimulant.

Under Investigation

SLU-PP-332 is not FDA-approved, and human studies are still in early phases. Use should be supervised by a licensed, peptide-trained clinician under an informed consent protocol.

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Comparison to Other Peptides

Peptide	Primary Benefit	Route	Cycle?
SLU-PP-332	Exercise mimetic, mitochondria, metabolic health	Oral	No
MOTS-c	Fat oxidation, mitochondrial resilience	Injection	No
Tesamorelin	Visceral fat loss	Injection	Yes
AOD-9604	Fat loss	Oral or injection	Yes
GHK-Cu	Anti-aging, skin, wound healing	Injection	Yes

SLU-PP-332 is especially attractive for those who want daily mitochondrial support without needles or cycling schedules.

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Final Thoughts

SLU-PP-332 represents a remarkable advancement in metabolic and mitochondrial medicine. As an oral, non-cycling peptide, it provides:

• The benefits of exercise—without the strain

• Restoration of mitochondrial capacity

• Improvements in insulin sensitivity, fat metabolism, and endurance

• Protection against age-related decline, inflammation, and cardiometabolic disease

Whether you're aging, dealing with insulin resistance, or just want to optimize your energy and longevity, this peptide has extraordinary potential.

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Call to Action

Interested in SLU-PP-332 for your metabolic health, longevity, or energy support? Revolution Health offers physician-supervised peptide programs that include advanced metabolic testing, dosing guidance, and customized protocols.

Contact us today to see if SLU-PP-332 is right for you:
https://revolutionhealth.org/pages/contact

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References

1. Billon C, et al. Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS Chem Biol. 2023.

2. Xu W, et al. Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function. Circulation. 2023;149:227–250.

3. Wang X, et al. Estrogen-related receptor agonism reverses mitochondrial dysfunction and inflammation in the aging kidney. Am J Pathol. 2023.

4. Sitaula S, et al. ERRs and Metabolic Regulation: The Mitochondrial Link. Mol Cell Endocrinol. 2022.