Discovery study: the mitochondrial-derived peptide MOTS-c promoted metabolic homeostasis, improved insulin sensitivity, and reduced obesity in mice on a high-fat diet.
MOTS-c
Mitochondrial-derived peptide for metabolic health and exercise performance

Overview
Last reviewed: 2026-08-18
Identity & Aliases
Also known as
Status: Research compound - Mitochondrial peptide
Full composition (formula, molecular weight, sequence) in Quick Facts →
Research Areas
Available Evidence
Human data are observational: acute endurance exercise increases circulating MOTS-c levels, and exercise interventions modulate MOTS-c in various populations. An interventional trial (MOTS-MET) testing MOTS-c for insulin sensitivity in adults with prediabetes and overweight/obesity is registered at ClinicalTrials.gov (phase 2).
In mice, MOTS-c administration improves insulin sensitivity, protects against high-fat diet-induced obesity and metabolic dysfunction, and promotes metabolic homeostasis, per the discovery study in Cell Metabolism.
Cell studies show MOTS-c translocates to the nucleus under metabolic stress to regulate gene expression, including AMPK pathway activation, supporting a role in metabolic adaptation.
Claims that MOTS-c is an 'exercise mimetic' or anti-aging peptide for humans are not established; effects of exogenous MOTS-c in people await results of the ongoing clinical trial.
Key Studies & Findings
Acute endurance exercise significantly increased circulating levels of mitochondrial-derived peptides, including MOTS-c, in humans.
A phase 2 trial (MOTS-MET) is registered to test whether MOTS-c improves insulin sensitivity in adults with prediabetes and overweight/obesity.
Benefits & Effects
Side Effects & Safety
Limitations & Open Questions
Pharmacology
Reported Research Dosing
Reported values from research literature and community protocols. Educational reference only — not a dosing recommendation or medical advice.
5-10mg 3x weekly
Research Protocols
Metabolic health
- Dose
- 5-10mg
- Frequency
- Once daily
- Route
- Subcutaneous
Anti-aging protocol
- Dose
- 15mg
- Frequency
- 3x weekly
- Route
- Subcutaneous
Exercise performance
- Dose
- 10-15mg
- Frequency
- Pre-workout
- Route
- Subcutaneous
Conservative start
- Dose
- 5mg
- Frequency
- Once daily
- Route
- Subcutaneous
Research protocols are for educational purposes only. Always consult qualified medical professionals.
Frequently Asked Questions
Is MOTS-c proven to improve metabolism in humans?
Not yet - human evidence is observational, and the first interventional trial (MOTS-MET) is ongoing.
Is MOTS-c an exercise mimetic?
Exercise increases circulating MOTS-c, but whether giving the peptide reproduces exercise benefits in people is unproven.
Is MOTS-c FDA approved?
No; it is an investigational peptide with a registered phase 2 trial at ClinicalTrials.gov.
Research Citations
Kong BS, Lee C, Cho YM (2023)
Gao Y, Wei X, Wei P, Lu H, Zhong L, Tan J, Liu H, Liu Z (2023)
Kumagai H, Coelho AR, Wan J, Mehta HH, Yen K, Huang A, Zempo H, Fuku N, Maeda S, Oliveira PJ, Cohen P, Kim SJ (2021)
Zheng Y, Wei Z, Wang T (2023)
+ 34 more citations
Related Resources
Quick Facts
Formula
C101H152N28O22S2
Molecular Weight
2174.61
Sequence
MRWQEMGYIFYPRKLR
Mechanism
Mitochondrial-derived peptide that regulates metabolic homeostasis
Safety Information
Research compound only. Limited human safety data available.
Citations
39Kong BS, Lee C, Cho YM (2023)
Gao Y, Wei X, Wei P, Lu H, Zhong L, Tan J, Liu H, Liu Z (2023)
Kumagai H, Coelho AR, Wan J, Mehta HH, Yen K, Huang A, Zempo H, Fuku N, Maeda S, Oliveira PJ, Cohen P, Kim SJ (2021)
Zheng Y, Wei Z, Wang T (2023)
+ 34 more citations