MOTS-c Research Evidence
The MOTS-c evidence base: trials, journals, and what the data does not yet show.
Key Findings at a Glance
• MOTS-c is one of the first peptides discovered to be encoded by mitochondrial DNA rather than nuclear DNA, revealing that mitochondria actively communicate with the rest of the cell through signaling molecules. • MOTS-c activates the AMPK pathway and enhances glucose uptake into skeletal muscle, closely mimicking the metabolic effects of physical exercise and earning it the label of exercise mimetic. • Circulating MOTS-c levels increase during exercise in humans, suggesting the peptide may naturally mediate some of the metabolic benefits attributed to physical activity. • MOTS-c has demonstrated the ability to prevent diet-induced obesity in animal models even without changes in food intake, by increasing energy expenditure and improving insulin sensitivity.
Exercise Mimetic Effects
Groundbreaking research has established MOTS-c as an exercise-induced mitochondrial peptide that may replicate some of the metabolic benefits of physical activity, leading to its classification as a potential exercise mimetic compound. Studies demonstrate that circulating MOTS-c levels increase significantly during exercise in both young and older individuals, with the peptide appearing to mediate some of exercise's beneficial effects on glucose metabolism and insulin sensitivity. Animal studies have shown that MOTS-c administration improves running endurance, enhances exercise capacity, and activates skeletal muscle adaptations similar to those produced by endurance training. The peptide's effects appear particularly relevant for aging populations, as research indicates MOTS-c may help maintain metabolic health and physical function in contexts where exercise capacity is limited. These exercise mimetic properties have generated significant interest in MOTS-c for research into aging interventions, physical performance optimization, and therapeutic approaches for individuals unable to exercise due to disability or illness.
Trials and reviews
- Reynolds plasma + muscle MOTS-c response to exerciseNat Commun2021
+1.6x plasma · +12x muscle MOTS-c after acute exercise · observational only, not interventional · N=10
References
- The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis · Lee C, et al. · 2015
- ClinicalTrials.gov: A Phase 1a/1b Study of CB4211 in Healthy Non-obese Subjects and Subjects With Nonalcoholic Fatty Liver Disease
- MOTS-c is an exercise-induced mitochondrial-encoded regulator of ...
- Mots-c | C101H152N28O22S2 | CID 146675088 - PubChem
- The Mitochondrial-Encoded Peptide MOTS-c Translocates to the ...
- MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation · Zheng Y, Wei Z, Wang T · 2023
- Mitochondria-derived peptide MOTS-c: effects and mechanisms ... · Wan W, Zhang L, Lin Y, Rao X, Wang X, Hua F, Ying J · 2023
- MOTS-c Functionally Prevents Metabolic Disorders · Gao Y, Wei X, Wei P, Lu H, Zhong L, Tan J, Liu H, Liu Z · 2023
- The mitochondrial-derived peptide MOTS-c relieves hyperglycemia ... · Yin Y, Pan Y, He J, Zhong H, Wu Y, Ji C, Liu L, Cui X · 2022
- MOTS-c: an equal opportunity insulin sensitizer - PMC · Kim SJ, Miller B, Kumagai H, Yen K, Cohen P · 2019
- The Mitochondrial-Encoded Peptide MOTS-c Translocates to ... - NIH · Kim KH, Son JM, Benayoun BA, Lee C · 2018
- MOTS-c: A Mitochondrial-Encoded Regulator of the Nucleus - PMC · Benayoun BA, Lee C · 2019