What it is
MOTS-c is a 16-amino-acid peptide encoded inside the mitochondrial 12S rRNA gene, one of the mitochondrial-derived peptides. It is produced by the body and can also be made synthetically. It appears in research on metabolism, skeletal muscle, exercise physiology, and ageing.
How it works
In rodent work MOTS-c is proposed to inhibit the folate cycle and de novo purine biosynthesis, which activates AMPK in skeletal muscle. It has also been reported to move into the nucleus and influence stress-responsive nuclear genes, and neither mechanism is settled.
Regulatory status
- Cosmetic ingredient
- Research compound
- In clinical trials
- Approved medicine
Not approved as a medicine by the FDA or the EMA. Some are registered in individual countries. Supplied for laboratory research only.
What published research is studying
- Insulin sensitivity and diet-induced obesity in rodent models
- Skeletal muscle metabolism and physical capacity in ageing mice
- The rise in endogenous MOTS-c in human skeletal muscle and blood after exercise
- Associations between circulating MOTS-c and body fat distribution in humans
Key findings
In mice, MOTS-c administration reduced diet-induced obesity and insulin resistance, alongside AMPK activation in skeletal muscle.
Lee C et al., Cell Metab 2015In mice aged 2, 12, and 22 months, MOTS-c administration improved physical performance, and intermittent dosing begun at 23.5 months increased physical capacity.
Reynolds JC et al., Nat Commun 2021In the same paper, exercise in human volunteers raised endogenous MOTS-c expression in skeletal muscle and in circulation.
Reynolds JC et al., Nat Commun 2021In a randomised 16-week aerobic and resistance exercise trial in 49 breast cancer survivors, plasma MOTS-c rose significantly in non-Hispanic White participants but not in Hispanic participants.
Dieli-Conwright CM et al., Sci Rep 2021
What the studies measured
Study durations
- Exercise trial measuring endogenous MOTS-c in survivors of breast cancer: 16 weeks.
- Late-life mouse study: intermittent dosing 3 times weekly, begun at 23.5 months of age (Reynolds et al. 2021).
- Cross-sectional human study of plasma MOTS-c: single timepoint in 125 adults without diabetes (Sequeira et al. 2021).
Endpoints
- Plasma MOTS-c concentration
- Whole-body insulin sensitivity by glucose infusion rate in mice
- Body weight and fat mass in rodent models
- Running and physical performance measures in mice
- Body fat distribution by DXA and magnetic resonance imaging
How strong is the evidence?
No published randomised trial has given MOTS-c to humans. The human data are observational and measure the body's own MOTS-c levels, while all dosing results come from mice.
Common questions
Is MOTS-c an approved medicine?
Research compound. Not approved as a medicine by the FDA or the EMA. Some are registered in individual countries. Supplied for laboratory research only.
How much human research is there on MOTS-c?
No published randomised trial has given MOTS-c to humans. The human data are observational and measure the body's own MOTS-c levels, while all dosing results come from mice.
Does UU supply MOTS-c?
Yes, as premium-grade research material for laboratory use. Every batch is tested by an independent lab and the certificate of analysis is published.