Skip to main content
SpringerLink
Log in

MOTS-c: an equal opportunity insulin sensitizer

  • Commentary
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P (2015) The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab 21:443–454

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Lee C, Kim KH, Cohen P (2016) MOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med 100:182–187

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lu H, Wei M, Zhai Y, Li Q, Ye Z, Wang L, Luo W, Chen J, Lu Z (2019) MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction. J Mol Med. https://doi.org/10.1007/s00109-018-01738-w

  4. Szmuilowicz ED, Stuenkel CA, Seely EW (2009) Influence of menopause on diabetes and diabetes risk. Nat Rev Endocrinol 5:553–558

    Article  PubMed  Google Scholar 

  5. Paschou SA, Anagnostis P, Pavlou DI et al (2018) Diabetes in menopause: risks and management. Curr Vasc Pharmacol 16:1–8

    Google Scholar 

  6. Watts NB (2018) postmenopausal osteoporosis: a clinical review. J Women’s Health (Larchmt) 27:1093–1096

    Article  Google Scholar 

  7. Venetsanaki V, Polyzos SA (2018) Menopause and non-alcoholic fatty liver disease: a review focusing on therapeutic perspectives. Curr Vasc Pharmacol 16:1–10

    Article  Google Scholar 

  8. Khoudary El SR, Thurston RC (2018) Cardiovascular implications of the menopause transition endogenous sex hormones and vasomotor symptoms. Obstet Gynecol Clin North Am 45:641–661

    Article  Google Scholar 

  9. Farah C, Kleindienst A, Bolea G, Meyer G, Gayrard S, Geny B, Obert P, Cazorla O, Tanguy S, Reboul C (2013) Exercise-induced cardioprotection: a role for eNOS uncoupling and NO metabolites. Basic Res Cardiol 108:389. https://doi.org/10.1007/s00395-013-0389-2

    Article  CAS  PubMed  Google Scholar 

  10. Golbidi S, Badran M, Laher I (2012) Antioxidant and anti-inflammatory effects of exercise in diabetic patients. Exp Diabetes Res 2012:941868–941816

    Article  CAS  PubMed  Google Scholar 

  11. Bueno-Notivol J, Calvo-Latorre J, Alonso-Ventura V, Pasupuleti V, Hernandez AV, Pérez-López FR (2017) Effect of programmed exercise on insulin sensitivity in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Menopause 24:1404–1413

    Article  PubMed  Google Scholar 

  12. Carnethon MR, Sternfeld B, Schreiner PJ, Jacobs DR, Lewis CE, Liu K, Sidney S (2009) Association of 20-year changes in cardiorespiratory fitness with incident type 2 diabetes: the coronary artery risk development in young adults (CARDIA) fitness study. Diabetes Care 32:1284–1288

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chen LY, Zmora R, Duval S, Chow LS, Lloyd-Jones DM, Schreiner PJ (2018) Cardiorespiratory fitness, adiposity, and heart rate variability: the CARDIA study. Med Sci Sports Exerc Publish Ahead of Print:1. https://doi.org/10.1249/MSS.0000000000001796

  14. Blair SN, Kohl HW, Paffenbarger RS et al (1989) Physical-fitness and all-cause mortality - a prospective-study of healthy-men and women. JAMA 262:2395–2401

    Article  CAS  PubMed  Google Scholar 

  15. Carlson SA, Fulton JE, Schoenborn CA, Loustalot F (2010) Trend and prevalence estimates based on the 2008 Physical Activity Guidelines for Americans. Am J Prev Med 39:305–313

    Article  PubMed  Google Scholar 

  16. Huh JY (2018) The role of exercise-induced myokines in regulating metabolism. Arch Pharm Res 41:14–29

    Article  CAS  PubMed  Google Scholar 

  17. Cantó C, Auwerx J (2009) PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure. Curr Opin Lipidol 20:98–105

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Fan W, Evans RM (2017) Exercise mimetics: impact on health and performance. Cell Metab 25:242–247

    Article  CAS  PubMed  Google Scholar 

  19. Grindstaff K, Magnan R, Shang R, Stenger E, Holland JS, Perez-Tilve D, Cundy KC (2018) CB4211 is a potential treatment for metabolic diseases with a novel mechanism of action—sensitization of the insulin receptor. Diabetes 67:233–LB. https://doi.org/10.2337/db18-233-LB

    Article  Google Scholar 

  20. Ming W, Lu G, Xin S, Huanyu L, Yinghao J, Xiaoying L, Chengming X, Banjun R, Li W, Zifan L (2016) Mitochondria related peptide MOTS-c suppresses ovariectomy-induced bone loss via AMPK activation. Biochem Biophys Res Commun 476:412–419

    Article  CAS  PubMed  Google Scholar 

  21. Hu B-T, Chen W-Z (2018) MOTS-c improves osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via TGF-β/Smad pathway. Eur Rev Med Pharmacol Sci 22:7156–7163

    PubMed  Google Scholar 

  22. Du C, Zhang C, Wu W et al (2018) Circulating MOTS-c levels are decreased in obese male children and adolescents and associated with insulin resistance. Pediatr Diabetes 19:1058–1064

    Article  CAS  Google Scholar 

  23. Cataldo LR, Fernández-Verdejo R, Santos JL, Galgani JE (2018) Plasma MOTS-c levels are associated with insulin sensitivity in lean but not in obese individuals. J Investig Med. https://doi.org/10.1136/jim-2017-000681

  24. Qin Q, Delrio S, Wan J, Jay Widmer R, Cohen P, Lerman LO, Lerman A (2018) Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction. Int J Cardiol 254:23–27

    Article  PubMed  Google Scholar 

  25. Zhai D, Ye Z, Jiang Y, Xu C, Ruan B, Yang Y, Lei X, Xiang A, Lu H, Zhu Z, Yan Z, Wei D, Li Q, Wang L, Lu Z (2017) MOTS-c peptide increases survival and decreases bacterial load in mice infected with MRSA. Mol Immunol 92:151–160

    Article  CAS  PubMed  Google Scholar 

  26. Yen K, Lee C, Mehta H, Cohen P (2013) The emerging role of the mitochondrial-derived peptide humanin in stress resistance. J Mol Endocrinol 50:R11–R19

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Kim SJ, Xiao J, Wan J, Cohen P, Yen K (2017) Mitochondrially derived peptides as novel regulators of metabolism. J Physiol Lond 595:6613–6621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Paharkova V, Alvarez G, Nakamura H, Cohen P, Lee KW (2015) Rat humanin is encoded and translated in mitochondria and is localized to the mitochondrial compartment where it regulates ROS production. Mol Cell Endocrinol 413:96–100

    Article  CAS  PubMed  Google Scholar 

  29. Sreekumar PG, Ishikawa K, Spee C, Mehta HH, Wan J, Yen K, Cohen P, Kannan R, Hinton DR (2016) The mitochondrial-derived peptide humanin protects RPE cells from oxidative stress, senescence, and mitochondrial dysfunction. Invest Ophthalmol Vis Sci 57:1238–1253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Kim SJ, Mehta HH, Wan J, Kuehnemann C, Chen J, Hu JF, Hoffman AR, Cohen P (2018) Mitochondrial peptides modulate mitochondrial function during cellular senescence. Aging (Albany NY) 10:1239–1256

    Article  CAS  Google Scholar 

  31. Nashine S, Cohen P, Chwa M, Lu S, Nesburn AB, Kuppermann BD, Kenney MC (2017) Humanin G (HNG) protects age-related macular degeneration (AMD) transmitochondrial ARPE-19 cybrids from mitochondrial and cellular damage. Cell Death Dis 8:e2951. https://doi.org/10.1038/cddis.2017.348

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hashimoto Y, Niikura T, Tajima H, Yasukawa T, Sudo H, Ito Y, Kita Y, Kawasumi M, Kouyama K, Doyu M, Sobue G, Koide T, Tsuji S, Lang J, Kurokawa K, Nishimoto I (2001) A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer’s disease genes and Abeta. Proc Natl Acad Sci U S A 98:6336–6341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Oh YK, Bachar AR, Zacharias DG, Kim SG, Wan J, Cobb LJ, Lerman LO, Cohen P, Lerman A (2011) Humanin preserves endothelial function and prevents atherosclerotic plaque progression in hypercholesterolemic ApoE deficient mice. Atherosclerosis 219:65–73

    Article  CAS  PubMed  Google Scholar 

  34. Cobb LJ, Lee C, Xiao J, Yen K, Wong RG, Nakamura HK, Mehta HH, Gao Q, Ashur C, Huffman DM, Wan J, Muzumdar R, Barzilai N, Cohen P (2016) Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers. Aging (Albany NY) 8:796–809

    Article  CAS  Google Scholar 

  35. Rathore A, Martinez TF, Chu Q, Saghatelian A (2018 Dec) Small, but mighty? Searching for human microproteins and their potential for understanding health and disease. Expert Rev Proteomics 15(12):963–965

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by a Glenn/AFAR Postdoctoral Fellowship Program for Translational Research on Aging to S.J.K and by grant P01AG034906 to P.C.

Author information

Authors and Affiliations

  1. Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, 90089-0191, USA

    Su-Jeong Kim, Brendan Miller, Hiroshi Kumagai, Kelvin Yen & Pinchas Cohen

Authors
  1. Su-Jeong Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Brendan Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroshi Kumagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kelvin Yen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pinchas Cohen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pinchas Cohen.

Ethics declarations

Conflict of interest

Drs. Kim, Miller, Kumagai and Yen report no conflicts. Pinchas Cohen is a consultant and stockholder of CohBar Inc.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kim, SJ., Miller, B., Kumagai, H. et al. MOTS-c: an equal opportunity insulin sensitizer. J Mol Med 97, 487–490 (2019). https://doi.org/10.1007/s00109-019-01758-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-019-01758-0

Search

Navigation