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May 13, 2025

Peptide Therapy - SLU-PP-332

SLU-PP-332 is associated with metabolic activation pathways, often studied in models exploring energy balance and endurance.

Peptide Therapy - SLU-PP-332

SLU-PP-332: A Promising Peptide for Metabolic Health and Exercise Mimicry

SLU-PP-332 is an investigational small molecule that has garnered attention in the scientific community for its potential to enhance metabolic health and mimic the effects of exercise. As a potent agonist of estrogen-related receptors (ERRs), particularly ERRα, SLU-PP-332 offers a novel approach to addressing metabolic disorders and age-related decline in mitochondrial function.

Mechanism of Action

SLU-PP-332 functions primarily as an agonist of the estrogen-related receptor alpha (ERRα), a nuclear receptor that plays a critical role in regulating energy metabolism. By binding to ERRα, SLU-PP-332 activates the receptor, leading to the upregulation of genes involved in:

  • Mitochondrial biogenesis: Enhancing the production of new mitochondria.

  • Oxidative phosphorylation: Improving the efficiency of the electron transport chain for ATP production.

  • Fatty acid oxidation: Increasing the breakdown of fatty acids for energy.

  • Glucose metabolism: Enhancing glucose uptake and utilization.

These effects collectively contribute to improved cellular energy homeostasis and metabolic function .

Benefits

1. Metabolic Health Improvement

Preclinical studies have demonstrated that SLU-PP-332 can significantly improve markers of metabolic health. In animal models of diet-induced obesity, treatment with SLU-PP-332 resulted in:

  • Reduction in body weight.

  • Decrease in white adipose tissue mass.

  • Improvement in glucose tolerance.

  • Lowering of fasting insulin levels.

  • Reduction in hepatic steatosis and inflammation .

2. Exercise Mimetic Effects

SLU-PP-332 has been shown to mimic the molecular and physiological effects of aerobic exercise. Notable findings include:

  • Increased mitochondrial density in skeletal muscle.

  • Enhanced expression of glucose transporters (e.g., GLUT4).

  • Improved muscular endurance and running capacity in sedentary animals.

  • Shift in muscle fiber composition toward more oxidative phenotypes.

  • Increased vascular density in skeletal muscle .

3. Mitochondrial Function and Aging

Aging is associated with a decline in mitochondrial function and increased inflammation. SLU-PP-332 has demonstrated the ability to:

  • Restore mitochondrial respiration rates in aged tissues.

  • Reduce age-associated inflammation markers such as IL-6 and TNF-α.

  • Decrease oxidative damage to mitochondrial DNA.

  • Improve autophagy and mitophagy processes.

  • Attenuate fibrotic changes in kidneys and heart .

4. Cardioprotective Effects

In models of heart failure and ischemia-reperfusion injury, SLU-PP-332 treatment led to:

  • Preservation of cardiac contractility.

  • Reduction in cardiomyocyte apoptosis.

  • Improved myocardial energetics through enhanced fatty acid oxidation.

  • Attenuation of pathological cardiac remodeling.

Scientific Evidence

The promising effects of SLU-PP-332 have been documented in several peer-reviewed studies:

  • Billon et al. (2023): Demonstrated that SLU-PP-332 induces an ERRα-dependent acute aerobic exercise response and enhances exercise capacity in mice.

  • Xu et al. (2023): Reported that novel pan-ERR agonists, including SLU-PP-332, ameliorate heart failure by enhancing cardiac fatty acid metabolism and mitochondrial function.

  • Wang et al. (2023): Found that estrogen-related receptor agonism reverses mitochondrial dysfunction and inflammation in the aging kidney .

Conclusion

SLU-PP-332 represents a promising therapeutic candidate for addressing metabolic disorders, enhancing exercise capacity, and mitigating age-related mitochondrial decline. While current findings are based on preclinical studies, the compelling evidence warrants further investigation into its potential applications in human health.

References

  1. Billon, C., Sitaula, S., Banerjee, S., et al. (2023). Synthetic ERRα/β/γ Agonist Induces an ERRα-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS Chemical Biology. https://doi.org/10.1021/acschembio.2c00720

  2. Xu, W., Billon, C., Li, H., et al. (2023). Novel Pan-ERR Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism and Mitochondrial Function. Circulation, 149, 227–250. https://doi.org/10.1161/CIRCULATIONAHA.123.066542

  3. Wang, X., Myakala, K., Libby, A., et al. (2023). Estrogen-related receptor agonism reverses mitochondrial dysfunction and inflammation in the aging kidney. The American Journal of Pathology. https://doi.org/10.1016/j.ajpath.2023.07.008

Note: SLU-PP-332 is currently under investigation and is not approved for clinical use. All information presented is based on preclinical research.