SLU p332 Overview and Applications

Overview

This lecture covers SLU p332, a mitochondrial peptide and estrogen-related receptor agonist, with emphasis on its mechanisms, applications, benefits, potential side effects, and dosing strategies.

History and Development of SLU p332

• SLU p332 is an estrogen-related receptor (ERR) agonist, primarily targeting the alpha subtype.
• Originated from modifications to the compound GSK 4716 to enhance alpha receptor activation.
• Early research indicated knockout of alpha ERR reduced muscle mass but didn't cause life-threatening issues.
• Gained popularity due to effectiveness for kidney, liver issues, and legality in sports.

Mitochondrial Structure and Function

• Mitochondria have outer/inner membranes, an intermembrane space, and matrix containing mitochondrial DNA.
• Surface area (via cristae) aids in cellular chemical signaling and metabolic processes.
• Protein import into mitochondria involves TOM and TIM complexes, requiring chaperone proteins for correct folding.

Estrogen-Related Receptors (ERRs) and Action Mechanisms

• ERRs are orphan nuclear receptors with no natural ligand; cholesterol and post-translational modifications regulate their activity.
• ERR alpha influences muscle, cardiac, and energetic tissues; beta influences cell proliferation; gamma impacts mitochondria and the brain.
• Activation can occur via acetylation, phosphorylation, and SUMOylation rather than direct ligand binding.

Biochemical Pathways and Crosstalk

• ERRs interact with PGC1-alpha, AMPK, and other metabolic signaling axes.
• Fasting and caloric deficit upregulate PGC1-alpha, enhancing ERR alpha activity, mitochondrial function, and cardiac resilience.
• Drugs like metformin also increase ERR activity through interconnected pathways.

Applications and Systemic Benefits of SLU p332

• Stimulates bone marrow stem cell release and enhances outcomes of stem cell therapies.
• Promotes muscle hypertrophy by increasing glycolytic fibers and glycogen storage.
• Facilitates lipolysis and fat oxidation even in parasympathetic states, aiding fat loss.
• Improves ATP recycling for strength athletes and supports endurance via better CO2/O2 handling.
• Supports cardiac function (ejection fraction, reduces fibrosis), renal function (GFR), and hepatic health (improves liver enzymes).
• Acts as a neuroprotective and anti-inflammatory agent, modulating neurotransmitters.
• May enhance ocular clarity and address sexual dysfunction in males (erectile function) and females (sensitivity).

Side Effects and Safety Considerations

• Rare cases of gynecomastia, tachycardia (increased heart rate), and overproduction of reactive oxygen species (ROS) due to excessive mitochondrial activity.
• Excessive dosing may blunt adaptation by minimizing necessary stress responses.
• Oral SLU p332 is as effective as other delivery methods.

Dosing Strategies

• Individual reference range is crucial; optimal response typically between 100 mcg and 1 mg daily.
• Athletes generally require lower doses (100–400+ mcg); dysfunctional/sick populations may need higher (400+ mcg to 1 mg).
• Gradually titrate dose upward while monitoring for benefits and side effects.
• Minimal added benefit and more side effects above 1 mg.

Key Terms & Definitions

• SLU p332 — A synthetic mitochondrial peptide acting as an ERR agonist.
• Estrogen-Related Receptors (ERRs) — Nuclear receptors modulating metabolism, not directly binding estrogen.
• Mitochondria — Cell organelles responsible for energy production, signaling, and metabolic regulation.
• PGC1-alpha — Peroxisome proliferator-activated receptor-gamma coactivator, a regulator of mitochondrial biogenesis.
• Reactive Oxygen Species (ROS) — Byproducts of mitochondrial activity that, in excess, can cause cellular damage.

Action Items / Next Steps

• Review mitochondrial structure and ERR function.
• Assess potential use cases or contraindications for SLU p332.
• If considering SLU p332, start at 100 mcg and titrate dose upward under supervision.
• Monitor for side effects (gynecomastia, tachycardia, fatigue).
• Explore further readings on mitochondrial peptides and ERR agonists.