Overview
Of estrogen receptor-related receptors (ERRs), SLU-PP-332 represents a synthetic agonist. In cellular energy regulation, ERRs are involved as nuclear receptors, serving as molecular targets for this compound studied in preclinical research.
Estrogen-Related Receptors (ERRs)
ERR Function
As transcription factors, ERRs function as orphan nuclear receptors, regulating genes involved in cellular energy homeostasis. Endogenous estrogens are not bound despite structural homology with estrogen receptors (ERs).
Three isoforms exist:
- ERRα (NR3B1)
- ERRβ (NR3B2)
- ERRγ (NR3B3)
These regulate:
- Glucose metabolism pathways
- Fatty acid oxidation
- Mitochondrial biogenesis
- Oxidative phosphorylation
Isoform Distribution
- In skeletal muscle, liver, heart, and brown adipose tissue, ERRα is highly expressed
- In cardiac and skeletal muscle tissue, ERRγ is abundant
- For embryonic stem cell pluripotency, ERRβ is important
Laboratory Effects Observed
Mitochondrial Function
In skeletal muscle cell lines, mitochondrial respiration is stimulated by SLU-PP-332. Pyruvate dehydrogenase kinase 4 (Pdk4) expression, a key ERR target gene, is promoted.
Linked to ATP synthesis pathways, increased mitochondrial respiration in C2C12 myocytes is demonstrated by studies.
Muscle Fiber Composition
In murine skeletal muscle, oxidative fiber proportion is increased by SLU-PP-332 administration, as shown by experimental studies. With alterations in endurance capacity measurements, this adaptation has been correlated.
Tissue Distribution
Beyond skeletal muscle, in cardiac tissue (affecting mitochondrial biogenesis) and neural tissue (involving neuronal energy homeostasis), ERR activity may be influenced by SLU-PP-332.
Preclinical Research Data
Compared to controls, alterations in body composition were shown by mice treated with SLU-PP-332, despite identical food consumption patterns, as reported by Billon et al.
To various physiological parameters in animal models, whether SLU-PP-332’s metabolic effects might relate is examined by research.
References:
- Billon, C., et al. (2023). Synthetic ERR agonist in exercise models. ACS Chem Biol, 18, 756-771.
- Billon, C., et al. (2024). ERR agonist in laboratory studies. J Pharmacol Exp Ther, 388(2), 232-240.
- Wang, X. X., et al. (2023). Receptor agonism in laboratory models. Am J Pathol, 193, 1969-1987.
