MOTS-c

Mitochondrial-derived peptide that activates AMPK and supports metabolic flexibility, insulin sensitivity, and exercise capacity.

Quick Reference

Dose: 5–10 mg
Frequency / schedule: 2–3× weekly or short pulsed courses
Route: Subcutaneous
Timing: Morning preferred
Fasting: Best fasted or before activity
Cycle: 6–12 weeks or short pulsed cycles (e.g., 4 injections over 20 days) repeated 2–4× per year
Time off: Equal time off or multi-month breaks between pulsed courses
Common vial strengths: 10 mg, 20 mg

How this works

MOTS-c is a 16-amino-acid peptide encoded by the mitochondrial genome. It inhibits the folate cycle, raising AICAR levels and activating AMPK. This improves glucose uptake (via GLUT4), enhances fatty-acid oxidation, and supports mitochondrial biogenesis and stress resistance. In animal models it improves insulin sensitivity, protects against diet-induced obesity, and increases physical capacity even in aged subjects.

Benefits + side effects

Potential Benefits

Improved glucose tolerance and insulin sensitivity (animal data)
Enhanced exercise capacity and metabolic flexibility
Potential age-related metabolic benefits

Side Effects

Injection-site reactions (common)
Occasional fatigue, headache, or transient jitteriness
Limited long-term human safety data

Dosing / Protocol

Reference Protocol

Phase / week	Dose	Frequency	Timing	Notes
Standard	5–10 mg	2–3× weekly	Morning	Most common continuous style
Pulsed	5 mg	Every 5 days × 4	Morning	Short course option

Timing + Fasting Notes

Morning, ideally fasted or before training/activity. Food is not strictly prohibited but fasted administration is preferred for metabolic signaling.

Reconstitution

Common vial strengths10 mg, 20 mg

Approved preparation example
Calculate carefully; use soon after mixing due to lower stability.

Practical Reference

Storage: Lyophilized frozen; reconstituted refrigerated and use within ~7 days preferred
Route / injection context: Subcutaneous
Bloodwork / markers: Fasting glucose, insulin, HbA1c, lipids
Common vial strengths: 10 mg, 20 mg
Cycle / time off: 6–12 weeks or short pulsed cycles (e.g., 4 injections over 20 days) repeated 2–4× per year · Equal time off or multi-month breaks between pulsed courses
Practical notes: Less stable after reconstitution than most peptides — plan usage accordingly. Research use only.

References

The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistanceCell Metabolism · 2015

PRECLINICAL02

MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolismFree Radical Biology and Medicine · 2016

REVIEW03

The mitochondrial-derived peptide MOTS-c is a regulator of plasma metabolites and enhances insulin sensitivityPhysiological Reports · 2019 · DOI 10.14814/phy2.14171

PRECLINICAL04

MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasisNature Communications · 2021

HUMAN

THE SIGNAL · SENT TWICE A MONTH

Stay ahead of the research without living on PubMed.

Peptide references, research worth knowing, new FEMETRIC tools, and meaningful testing updates. Twice a month. No daily emails.By subscribing, you agree to receive The Signal from FEMETRIC. Unsubscribe anytime.

Search Femetric