MOTS-c Spray

Research-Documented Benefits

• Metabolic Regulation — MOTS-c, a 16-amino acid mitochondrial-derived peptide, activates AMPK and improves glucose uptake independent of insulin signaling.
• Insulin Sensitivity — Research demonstrates improved insulin sensitivity and prevention of age-dependent and high-fat-diet-induced insulin resistance in rodent models.
• Exercise Physiology — Studies show MOTS-c translocates to the nucleus during metabolic stress, regulating gene expression related to cellular adaptation to exercise.
• Anti-Obesity Effects — Preclinical studies document reduced weight gain and improved metabolic profiles even on high-fat diets, without changes in food intake.
• Longevity Research — Endogenous MOTS-c levels decline with age; supplementation in aged mice improved physical capacity and metabolic homeostasis.

Mechanism of Action

MOTS-c (Mitochondrial Open reading frame of the Twelve S rRNA type-c) is a 16-amino acid peptide encoded within the mitochondrial 12S rRNA gene, representing a novel class of mitochondrial-derived signaling peptides.

Primary Pathways

• AMPK Activation — MOTS-c activates AMP-activated protein kinase, the master energy sensor that switches cells from anabolic to catabolic metabolism, enhancing fatty acid oxidation and glucose uptake.
• Folate-Methionine Cycle — Inhibits the folate cycle at the level of AICAR transformylase, leading to AICAR accumulation and secondary AMPK activation—a unique mechanism among peptide hormones.
• Nuclear Translocation — During metabolic stress (e.g., exercise), MOTS-c translocates from mitochondria to the nucleus where it regulates gene expression by interacting with ARE (antioxidant response element) motifs.
• Insulin-Independent Glucose Uptake — Promotes GLUT4 translocation to the cell surface via AMPK-mediated signaling, enhancing glucose uptake without requiring insulin receptor activation.

MOTS-c represents a paradigm shift in endocrinology—a hormone encoded in mitochondrial DNA that communicates mitochondrial metabolic status to the nucleus and peripheral tissues.

Research Protocol Guidelines

All protocols described are for in vitro and in vivo research purposes only. Not for human use.

Reconstitution

Reconstitute lyophilized MOTS-c with bacteriostatic water. For a 5 mg vial, adding 1 mL yields 5 mg/mL.

Research Dosing (Preclinical Literature)

• Metabolic studies: 5-15 mg/kg/day intraperitoneally in murine obesity and diabetes models
• Exercise research: 5 mg/kg IP administered prior to or during exercise protocols in rodent models
• Aging studies: 5 mg/kg/day IP for 2-4 weeks in aged mice for physical performance and metabolic assessments
• In vitro: 1-10 uM in cell culture for AMPK activation and glucose uptake assays

Storage

Store lyophilized form at -20°C. Reconstituted at 2-8°C, use within 14 days. MOTS-c is a relatively stable 16-amino acid peptide but should be protected from repeated freeze-thaw cycles.

Safety & Handling Information

For research use only. Not intended for human or veterinary diagnostic or therapeutic use.

Storage Requirements

• Lyophilized: -20°C, desiccated
• Reconstituted: 2-8°C, use within 14 days

Preclinical Safety Profile

MOTS-c is an endogenous peptide present in human plasma. Preclinical studies at standard research doses (5-15 mg/kg in rodents) have not reported significant adverse effects on organ function or histopathology.

Known Considerations

• AMPK activation and metabolic effects may alter glucose homeostasis—monitor blood glucose in diabetic or metabolically challenged models
• Folate cycle disruption (via AICAR accumulation) may affect studies involving folate metabolism or one-carbon metabolism
• Nuclear translocation under stress conditions means MOTS-c directly influences gene expression—consider in transcriptomic study designs
• Endogenous MOTS-c levels vary by age, ethnicity, and metabolic status

Handling

Standard laboratory PPE. MOTS-c is a small, stable peptide with no unusual handling requirements.

Frequently Asked Questions