Dr. Grey AI

MOTS-c

Peptide

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a 16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA gene. Discovered in 2015, it regulates metabolic homeostasis, insulin sensitivity, and has been shown to mimic some beneficial effects of exercise. MOTS-c levels naturally decline with age, and the peptide is being studied for age-related metabolic diseases.

Quick Answer

What it is

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a 16-amino-acid mitochondrial-derived peptide encoded within the 12S rRNA gene. Discovered in 2015, it regulates metabolic homeostasis, insulin sensitivity, and has been shown to mimic some beneficial effects of exercise.

Key findings

  • Grade A: Insulin Sensitivity (Metabolic Health)
  • Grade A: Glucose Metabolism (Metabolic Health)
  • Grade B: Body Weight (Body Composition)

Safety

No specific caution or interaction language was detected in the current summary/outcome notes.

⚠️ Research Notice

This peptide information is for educational and research purposes only. Peptides may not be FDA-approved for human use and may only be legally available for research purposes. Consult qualified healthcare professionals before considering any peptide compounds.

ℹ️ Quick Facts: MOTS-c

Quick Facts: MOTS-c

  • Best Evidence:Grade A
  • Conditions Studied:4
  • Research Outcomes:27
  • Grade A Findings:2
  • Grade B Findings:7
  • Key Effect:Metabolic Health
A2
B7
C15
D3
4 conditions · 27 outcomes

Detailed Outcomes

|
A
Insulin Sensitivity
MOTS-c treatment prevented age-dependent and high-fat-diet-induced insulin resistance in mice. Human studies show plasma MOTS-c levels correlate positively with insulin sensitivity in lean individuals.
large↑Improves
A
Glucose Metabolism
MOTS-c improves glucose metabolism in skeletal muscle by enhancing GLUT4 translocation via AMPK activation, reducing hyperglycemia and hyperinsulinemia in diet-induced obese mice.
large↓Improves
B
Body Weight
MOTS-c treatment reduced diet-induced obesity in mice by increasing energy expenditure and decreasing fat accumulation, particularly in liver tissue.
moderate↓Improves
B
Fat Accumulation
MOTS-c significantly decreases hepatic fat accumulation and adipose tissue in high-fat diet fed animals, with improvements in liver lipid profiles.
moderate↓Improves
B
Physical Performance
MOTS-c significantly enhanced physical performance in young, middle-aged, and old mice. Late-life initiated intermittent treatment increased physical capacity and healthspan.
moderate↑Improves
B
Muscle Homeostasis
MOTS-c acts as an exercise-induced mitochondrial-encoded regulator of muscle homeostasis, reducing myostatin and muscle atrophy signaling pathways.
moderate↑Improves
B
Age-Related Insulin Resistance
Systemic MOTS-c injection restored peptide levels in aged mice and successfully reversed age-related skeletal muscle insulin resistance.
moderate↓Improves
B
MOTS-c Plasma Levels
Plasma MOTS-c levels decline with age in both mice and humans. Circulating levels are significantly lower in obese individuals and type 2 diabetes patients.
moderate↓Improves
B
Pancreatic Islet Cell Senescence
MOTS-c prevents pancreatic islet cell senescence and delays diabetes progression by acting as a senotherapeutic agent.
moderate↓Improves
C
Type 2 Diabetes Risk
In humans, serum MOTS-c levels are lower in patients with inadequately controlled T2DM (HbA1c >7%). Higher physical activity may rescue metabolic effects in individuals with certain mtDNA polymorphisms.
moderate↓Improves
C
Blood Glucose Control
9 preclinical studies support this finding. Primarily preclinical evidence.
moderate↓Improves
C
Pulmonary Function
6 preclinical studies support this finding. Primarily preclinical evidence.
small↑Improves
C
Oxidative Stress
5 preclinical studies support this finding. Primarily preclinical evidence.
small↓Improves
C
Liver Protection
4 preclinical studies support this finding. Primarily preclinical evidence.
small↑Improves
C
Anti-Aging
3 preclinical studies support this finding. Primarily preclinical evidence.
small↑Improves
C
Bone Mineral Density
3 preclinical studies support this finding. Primarily preclinical evidence.
small↑Improves
C
Anti-Inflammatory Activity
3 preclinical studies support this finding. Primarily preclinical evidence.
small↑Improves
C
Neuroprotection
3 preclinical studies support this finding. Primarily preclinical evidence.
small↑Improves
C
Cancer Cell Apoptosis
3 preclinical studies support this finding. Primarily preclinical evidence.
small↑Improves
C
Endothelial Function
3 preclinical studies support this finding. Primarily preclinical evidence.
small↑Improves
C
Pain
3 preclinical studies support this finding. Primarily preclinical evidence.
small↓Improves
D
Lipid Profile
2 preclinical studies support this finding. Primarily preclinical evidence.
small↓Improves
D
Sepsis Outcomes
2 preclinical studies support this finding. Primarily preclinical evidence.
small↓Improves

Research Citations (73)

Mitochondrial-encoded peptide MOTS-c prevents pancreatic islet cell senescence to delay diabetes
(2025)
PMID: 40855115
MOTS-C levels ın ındividuals with and without obesity and ıts association with ınflammation, insulin resistance and endothelial dysfunction.
(2025)
PMID: 41004666
MOTS-c in type 2 diabetes mellitus: From risk factors to cardiac complications and potential treatment.
(2025)
PMID: 41083123
MOTS-c mimics remote ischemic preconditioning in protecting against lung ischemia-reperfusion injury by alleviating endothelial barrier dysfunction.
(2025)
PMID: 39827923
MOTS-c as a Potential Diagnostic-prognostic Biomarker for Myocardial Infarction.
(2025)
PMID: 40353474
MOTS-c relieves hepatocellular carcinoma resistance to TRAIL-induced apoptosis under hypoxic conditions by activating MEF2A.
(2025)
PMID: 39581216
MOTS-c attenuates lung ischemia-reperfusion injury via MYH9-Dependent nuclear translocation and transcriptional activation of antioxidant genes.
(2025)
PMID: 40403491
A mitochondrial-derived peptide MOTS-c contributes to the protective effect against brain injury associated with LPS-induced sepsis by strengthening the blood-brain barrier's ultrastructure.
(2025)
PMID: 40753494
MOTS-c attenuates airway barrier dysfunction in allergic asthma by inhibiting epithelial apoptosis via Nrf2 pathway.
(2025)
PMID: 40472776
MOTS-c Promotes Glycolysis via AMPK-HIF-1α-PFKFB3 Pathway to Ameliorate Cardiopulmonary Bypass-induced Lung Injury.
(2025)
PMID: 40035775