PMID-36988910 – SLU-PP-332 ERR Agonist Acute Exercise Response
Kim SH, Teng S, Ying Z, Gomez-Pinilla F, Bhatt S, Burris TP. Synthetic ERRalpha/beta/gamma Agonist Induces an ERRalpha-Dependent Acute Aerobic Exercise Response and Enhances Exercise Capacity. ACS Chem Biol. 2023;18(4):866-872.
Quick Reference
| Property | Value |
|---|---|
| PMID | 36988910 |
| DOI | 10.1021/acschembio.2c00720 |
| Year | 2023 |
| Journal | ACS Chemical Biology |
| Study Type | Animal in vivo |
| Evidence Level | V |
| Sample | Mice (wild-type and ERRalpha knockout) |
| Peptide(s) Studied | SLU-PP-332 |
Key Findings
- SLU-PP-332 activated an acute aerobic exercise transcriptional program in skeletal muscle
- Treatment increased type IIa (oxidative) muscle fibers at the expense of type IIb (glycolytic) fibers
- Exercise endurance was significantly enhanced (increased treadmill running time)
- The effects were ERRalpha-dependent — abolished in ERRalpha knockout mice
- PGC-1alpha co-activation downstream of ERR engagement drives mitochondrial biogenesis
- Gene expression profiling showed upregulation of mitochondrial OXPHOS and FAO pathways
- Muscle fiber type switching was verified by immunohistochemistry
Study Design
Preclinical study using wild-type and ERRalpha knockout mice. Animals treated with SLU-PP-332 IP and subjected to exercise performance testing (treadmill running), muscle fiber typing, and gene expression analysis.
Limitations
- Animal study only; no human data
- IP route of administration (not oral)
- Acute treatment effects; chronic dosing effects less characterized
- ERRalpha KO mice may have compensatory mechanisms affecting interpretation
- Single research group
Clinical Relevance
The foundational mechanistic study explaining how SLU-PP-332 works as an "exercise in a pill." The muscle fiber type switching from fast-twitch glycolytic to slow-twitch oxidative fibers mirrors the adaptation seen with endurance training. The ERRalpha-dependence confirms the target and provides a clear mechanistic pathway. Relevant for understanding the biological rationale, though clinical translation remains distant.
Related
#research #animal-in-vivo #SLU-PP-332 #evidence-level-V