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SS-LUP-332 Exercise Gene Program Activation: Compound Comparison
SS-LUP-332 PPARδ agonist → PGC-1α upregulation Strong—2.5× PGC-1α mRNA, sustained mitochondrial DNA increase Yes—Type I and IIa fiber markers elevated 44–68% improvement in sedentary rodents Most complete exercise mimetic—activates full transcriptional program
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- SS-LUP-332
- PPARδ agonist → PGC-1α upregulation
- Strong—2.5× PGC-1α mRNA, sustained mitochondrial DNA increase
- Yes—Type I and IIa fiber markers elevated
- 44–68% improvement in sedentary rodents
- Most complete exercise mimetic—activates full transcriptional program without contractile requirement
- AICAR
- Direct AMPK activation
- Weak—requires concurrent exercise for sustained effect
- Minimal—no consistent fiber-type gene expression changes
- 20–30% improvement, diminishes without training
- Effective acute metabolic switch but does not replicate training adaptations
- GW501516
- PPARδ agonist (first-generation)
- Strong—similar PGC-1α activation to SS-LUP-332
- Yes—comparable slow-twitch conversion
- 50–75% improvement in multiple studies
- Mechanistically sound but discontinued due to tumor signals at high chronic doses
- Metformin
- Complex I inhibition → AMPK activation
- Minimal—primarily acute AMPK signaling
- No—gene expression effects differ from training
- 0–15% improvement, inconsistent across studies
- Energy stress mimetic, not exercise mimetic—different transcriptional signature
- Resveratrol
- SIRT1 activation → PGC-1α deacetylation
- Moderate—inconsistent across dose ranges
- Weak—limited evidence for fiber-type remodeling
- 10–25% improvement at supraphysiological doses
- Partial pathway activation—does not replicate PPARδ-mediated oxidative gene program