MOTS-c (Human)

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1. Core Molecular & Physicochemical Specifications

2. Mechanism of Action

1. AMPK Activation: Inhibits the methionine - folate cycle, elevates AICAR (AMP analog), and activates AMPK to upregulate GLUT4, boosting glucose uptake and insulin sensitivity.
2. Mito - Nuclear Signaling: Translocates to the nucleus under metabolic stress (glucose restriction, oxidative stress) to regulate Nrf2, PGC - 1α, and antioxidant genes, enhancing stress resistance.
3. Metabolic Remodeling: Promotes fatty acid oxidation, reduces lipogenesis, and prevents diet - induced obesity by improving energy expenditure.
4. Tissue - Specific Effects: Enhances muscle mitochondrial biogenesis, protects cardiac function via antioxidant pathways, and mitigates NASH via Bcl - 2 stabilization.

3. Biological Functions & Application Fields

3.1 Core Physiological Effects

• Metabolic Regulation: Reduces fasting glucose (by ~35%), HOMA - IR (by ~40%), and triglycerides (by 25–30%) in diabetic rodent models; prevents diet - induced obesity.
• Muscle & Aging: Reverses age - dependent muscle insulin resistance, improves exercise capacity, and preserves muscle mass in aging mice.
• Antioxidant & Anti - Inflammatory: Upregulates SOD/GSH activity, reduces MDA, and inhibits pro - inflammatory cytokines (TNF - α, IL - 6).
• Organ Protection: Mitigates NASH progression, reduces cardiac mitochondrial damage, and supports bone metabolism.

3.2 Application Fields

4. Production & Quality Control

4.1 Manufacturing Processes

1. SPPS Synthesis: Fmoc - based solid - phase synthesis with Rink amide resin; purified by preparative RP - HPLC (C18 column, gradient elution).
2. Lyophilization: Freeze - dried to preserve activity; vacuum - sealed with desiccant to avoid moisture.
3. Quality Validation: Identity confirmed by mass spectrometry; purity verified via analytical HPLC; endotoxin tested via LAL assay.

4.2 Quality Testing Standards

5. Administration, Safety & Precautions

5.1 Administration Routes & Dosage

• Rodent Injection: Intraperitoneal (IP) 5–20 mg/kg/day for 4–8 weeks; subcutaneous (SC) 1–5 mg/kg 3x/week for metabolic studies.
• Cell Culture: 1–10 μM for in vitro glucose uptake or AMPK signaling assays.
• Combination Therapy: Synergizes with exercise to enhance glucose disposal and oxidative stress reduction.

5.2 Safety Profile

• Low Toxicity: LD₅₀ > 100 mg/kg in rodents; no acute organ toxicity reported.
• Minimal Side Effects: Transient injection - site irritation; no off - target effects in preclinical studies.
• Contraindications: Hypersensitivity to MOTS - c; caution in pregnant/lactating animals (limited data).
• Regulatory Status: Research use only; banned by WADA for athletic performance enhancement (2024 onwards).

5.3 Handling Guidelines

• Storage: Lyophilized powder at - 20°C; reconstituted solution at 4°C (avoid repeated freeze - thaw).
• Reconstitution: Use sterile water or PBS (pH 7.0–7.4); avoid mixing with high - salt buffers.
• Transport: Cold chain (2–8°C) to prevent degradation.

6. Key Advantages & Limitations

6.1 Advantages

1. Exercise - Mimetic Effects: Recapitulates metabolic benefits of exercise without physical training, ideal for sedentary/aged models.
2. Mito - Nuclear Coordinator: Unique ability to link mitochondrial stress to nuclear gene expression, enabling systemic homeostasis.
3. Multi - Organ Utility: Effective in metabolic, muscle, cardiac, and hepatic models, supporting cross - disciplinary research.
4. Well - Characterized: Extensive preclinical data on mechanism and efficacy, accelerating hypothesis testing.

6.2 Limitations

1. Short Half - Life: Plasma half - life ~30–60 minutes; requires frequent dosing or sustained - release formulations.
2. Species Specificity: Human sequence differs from murine; cross - species studies need sequence - matched peptides.
3. Preclinical Only: Limited human data; clinical translation requires dose - ranging and safety trials.

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