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Product Overview

MOTS-c Clinical Summary

MOTS-c is a 16–amino acid mitochondrial-derived peptide encoded by the 12S rRNA region of mitochondrial DNA. It acts as a metabolic regulator—primarily in skeletal muscle—and is increasingly recognized as a key signaling molecule for adaptation to metabolic stress.[1][2][3][4][5]

  • Metabolic regulation & mitochondrial efficiency: MOTS-c inhibits the folate cycle and de novo purine biosynthesis, activating AMPK to drive energy balance and mitochondrial biogenesis—improving mitochondrial efficiency and stress resilience.[1][6][2][3][7][4]
  • Fat metabolism & fat loss: In animals, MOTS-c prevents diet-induced obesity and age-related fat gain by increasing fatty-acid oxidation and reducing hepatic/adipose lipid deposition. It upregulates mitochondrial fusion genes (OPA1, MFN2) important for fat metabolism.[1][8][7]
  • Insulin sensitivity & blood sugar control: MOTS-c improves skeletal-muscle insulin sensitivity and glucose uptake via AMPK activation and GLUT4 translocation. Exercise and adiponectin boost MOTS-c through the APPL1–SIRT1–PGC-1α pathway.[1][6][7][3][4][9]
  • Energy levels & endurance: MOTS-c increases exercise capacity and endurance in mice, mimicking aerobic-exercise benefits (better insulin sensitivity, antioxidant capacity, weight loss). In humans, acute/chronic exercise elevates MOTS-c in muscle and plasma and correlates with metabolic and performance improvements.[10][11]
  • Cellular resilience & stress adaptation: Under metabolic stress, MOTS-c translocates to the nucleus to regulate stress-adaptation genes (including ARE-containing targets), promoting resilience and healthy aging.[2][4][5]
  • Clinical & translational implications: MOTS-c levels decline with age and metabolic disease but rise with exercise or exogenous dosing; it’s being investigated for obesity, diabetes, aging, cardiovascular disease, and cancer.[12][10][5][11][4]
  • Dosage: While 10 mg appears in research protocols, there is no established clinical dosing guideline in humans; most data are from animal or in vitro studies.[1][6][8]

Summary: MOTS-c is a mitochondrial-derived peptide with pleiotropic benefits across metabolic regulation, mitochondrial function, fat metabolism, insulin sensitivity, cellular resilience, and physical performance. Its mechanism centers on AMPK activation and mito-nuclear signaling, with translational potential for metabolic and age-related conditions.[1][6][2][12][7][3][10][4][5][11][9][8]

References

  1. Lee C, Zeng J, Drew BG, et al. Cell Metab. 2015;21(3):443-54. doi:10.1016/j.cmet.2015.02.009.
  2. Wan W, Zhang L, Lin Y, et al. J Transl Med. 2023;21(1):36. doi:10.1186/s12967-023-03885-2.
  3. Lee C, Kim KH, Cohen P. Free Radic Biol Med. 2016;100:182-187. doi:10.1016/j.freeradbiomed.2016.05.015.
  4. Zheng Y, Wei Z, Wang T. Front Endocrinol. 2023;14:1120533. doi:10.3389/fendo.2023.1120533.
  5. Mohtashami Z, Singh MK, Salimiaghdam N, Ozgul M, Kenney MC. Int J Mol Sci. 2022;23(19):11991. doi:10.3390/ijms231911991.
  6. Yang B, Yu Q, Chang B, et al. BBA-Mol Basis Dis. 2021;1867(6):166126. doi:10.1016/j.bbadis.2021.166126.
  7. Bhullar KS, Shang N, Kerek E, Wu K, Wu J. Sci Rep. 2021;11(1):14291. doi:10.1038/s41598-021-93735-2.
  8. Li Q, Lu H, Hu G, et al. Biochem Biophys Res Commun. 2019;513(2):439-445. doi:10.1016/j.bbrc.2019.03.194.
  9. Guo Q, Chang B, Yu QL, et al. Diabetologia. 2020;63(12):2675-2688. doi:10.1007/s00125-020-05269-3.
  10. Woodhead JST, Merry TL. BBA-Gen Subj. 2021;1865(12):130011. doi:10.1016/j.bbagen.2021.130011.
  11. Dieli-Conwright CM, Sami N, Norris MK, et al. Sci Rep. 2021;11(1):16916. doi:10.1038/s41598-021-96419-z.
  12. Merry TL, Chan A, Woodhead JST, et al. Am J Physiol Endocrinol Metab. 2020;319(4):E659-E666. doi:10.1152/ajpendo.00249.2020.

ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY. The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs and have not been approved by the FDA to prevent, treat or cure any medical condition, ailment or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.