Metabolic Modulators
MOTS-c
Mitochondria-encoded peptide that activates AMPK and acts like an 'exercise signal' in animals; human data are early.
Overview
MOTS-c is a 16-amino-acid peptide encoded by mitochondrial rather than nuclear DNA, part of a newly recognized class of 'mitokines' that let mitochondria signal the rest of the cell. Under metabolic stress, it activates AMPK, the cell's energy sensor, and can move to the nucleus to influence stress-response genes. In mice, it improves insulin sensitivity, protects against diet-induced weight gain, and boosts physical capacity in older animals. In humans, blood levels rise with exercise and fall with age, but controlled trials of MOTS-c itself have not been published. It is best viewed as a promising exercise-mimetic research peptide that works best alongside training.
- Classification
- 16-amino-acid mitochondrial-derived peptide (mitokine) encoded in mitochondrial DNA
- Route
- Subcutaneous
- Half-life
- ~1–2 hours (SC; limited data)
Mechanism of action
- Released under stressMitochondria produce MOTS-c during exercise and metabolic stress.
- Folate cycle inhibitionInhibits the folate cycle, raising the metabolite AICAR.
- AMPK activationAICAR accumulation activates AMPK, the master energy sensor.
- Glucose uptake risesIncreased GLUT4-mediated glucose uptake in skeletal muscle.
- Nuclear gene regulationTranslocates to nucleus, regulating antioxidant and stress-response genes.
- Improved insulin sensitivity
- Greater exercise capacity
- Resistance to weight gain
Researched for
- Insulin resistance and type 2 diabetes
- Obesity
- Age-related physical decline
- Exercise performance
- Osteoporosis (preclinical)
Research notes
- Discovery paper (Lee 2015, Cell Metab): MOTS-c prevented diet-induced obesity and insulin resistance in mice.
- Reynolds 2021 (Nat Commun): exercise raised MOTS-c in human muscle and plasma; treatment improved physical capacity in old mice.
- A related analog (CB4211) entered early-phase human trials for fatty liver and obesity; full results remain limited.
- No published randomized trials of MOTS-c itself in humans; optimal dosing is unknown.
Reported side effects
- Injection-site redness or itching
- Transient fatigue or flu-like feeling (reported)
- Possible low blood sugar with diabetes drugs
- Long-term effects unknown
Contraindications & cautions
- Pregnancy or breastfeeding
- Active malignancy
- Primary mitochondrial disease (specialist input)
- Recurrent hypoglycemia
Lab monitoring
- Fasting glucose, HbA1c, fasting insulin (HOMA-IR)
- Lipid panel
- CMP with liver enzymes
- Body composition
- Exercise capacity testing
Dosing and pricing for MOTS-c
Dosing references and compound pricing are available to established patients in the secure portal after a medical evaluation.
Ready to take control of your health?
Start with a 60-minute physician evaluation, virtually in seven states or in person in Reston, Virginia.
Cash-pay. HSA and FSA accepted. Monday–Friday, 10 AM – 2 PM (virtual and in person).