Display options
Cite
Ordelheide AM, Gommer N, Böhm A, et al. Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans. Mol Metab. 2016;5(4):305-316doi: 10.1016/j.molmet.2016.02.001.
Ordelheide, A. M., Gommer, N., Böhm, A., Hermann, C., Thielker, I., Machicao, F., Fritsche, A., Stefan, N., Häring, H. U., & Staiger, H. (2016). Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans. Molecular metabolism, 5(4), 305-316. https://doi.org/10.1016/j.molmet.2016.02.001
Ordelheide, Anna-Maria, et al. "Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans." Molecular metabolism vol. 5,4 (2016): 305-316. doi: https://doi.org/10.1016/j.molmet.2016.02.001
Ordelheide AM, Gommer N, Böhm A, Hermann C, Thielker I, Machicao F, Fritsche A, Stefan N, Häring HU, Staiger H. Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans. Mol Metab. 2016 Feb 13;5(4):305-316. doi: 10.1016/j.molmet.2016.02.001. eCollection 2016 Apr. PMID: 27069870; PMCID: PMC4812007.
Copy Download .nbib Format: NLM
Share it on

Mol Metab. 2016 Feb 13;5(4):305-316. doi: 10.1016/j.molmet.2016.02.001. eCollection 2016 Apr.

Granulocyte colony-stimulating factor (G-CSF): A saturated fatty acid-induced myokine with insulin-desensitizing properties in humans.

Molecular metabolism

Anna-Maria Ordelheide, Nadja Gommer, Anja Böhm, Carina Hermann, Inga Thielker, Fausto Machicao, Andreas Fritsche, Norbert Stefan, Hans-Ulrich Häring, Harald Staiger

Affiliations

  1. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany.
  2. Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany.
  3. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany.
  4. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany; Department of Internal Medicine, Division of Nutritional and Preventive Medicine, University Hospital Tübingen, Tübingen, Germany.
  5. Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Department of Internal Medicine, Division of Endocrinology, Diabetology, Angiology, Nephrology and Clinical Chemistry, University Hospital Tübingen, Tübingen, Germany. Electronic address: [email protected].

PMID: 27069870 PMCID: PMC4812007 DOI: 10.1016/j.molmet.2016.02.001

Abstract

OBJECTIVE: Circulating long-chain free fatty acids (FFAs) are important metabolic signals that acutely enhance fatty acid oxidation, thermogenesis, energy expenditure, and insulin secretion. However, if chronically elevated, they provoke inflammation, insulin resistance, and β-cell failure. Moreover, FFAs act via multiple signaling pathways as very potent regulators of gene expression. In human skeletal muscle cells differentiated in vitro (myotubes), we have shown in previous studies that the expression of CSF3, the gene encoding granulocyte colony-stimulating factor (G-CSF), is markedly induced upon FFA treatment and exercise.

METHODS AND RESULTS: We now report that CSF3 is induced in human myotubes by saturated, but not unsaturated, FFAs via Toll-like receptor 4-dependent and -independent pathways including activation of Rel-A, AP-1, C/EBPα, Src, and stress kinases. Furthermore, we show that human adipocytes and myotubes treated with G-CSF become insulin-resistant. In line with this, a functional polymorphism in the CSF3 gene affects adipose tissue- and whole-body insulin sensitivity and glucose tolerance in human subjects with elevated plasma FFA concentrations.

CONCLUSION: G-CSF emerges as a new player in FFA-induced insulin resistance and thus may be of interest as a target for prevention and treatment of type 2 diabetes.

Keywords: Fatty acid-induced insulin resistance; Granulocyte colony-stimulating factor (G-CSF); Saturated fatty acid-induced myokine

References

  1. Eur J Immunol. 2003 Mar;33(3):798-805 - PubMed
  2. PLoS One. 2011;6(6):e21594 - PubMed
  3. Diabetes. 2008 Oct;57(10 ):2595-602 - PubMed
  4. PLoS One. 2012;7(1):e29880 - PubMed
  5. Cell. 2011 Sep 30;147(1):173-84 - PubMed
  6. PLoS One. 2012;7(10):e48155 - PubMed
  7. J Biol Chem. 2001 May 18;276(20):16683-9 - PubMed
  8. Diabetes Care. 1999 Sep;22(9):1462-70 - PubMed
  9. Diabetes. 2006 Nov;55(11):3121-6 - PubMed
  10. J Clin Invest. 2006 Nov;116(11):3015-25 - PubMed
  11. Diabetes Care. 2010 Feb;33(2):405-7 - PubMed
  12. J Biol Chem. 2003 Sep 26;278(39):37041-51 - PubMed
  13. Mol Pharmacol. 2011 Jan;79(1):34-41 - PubMed
  14. Biochem Soc Trans. 2008 Oct;36(Pt 5):909-15 - PubMed
  15. Lancet. 1989 Oct 14;2(8668):891-5 - PubMed
  16. Med Sci Sports Exerc. 2012 Aug;44(8):1463-72 - PubMed
  17. Lancet. 1992 Mar 14;339(8794):640-4 - PubMed
  18. Nature. 2006 Dec 14;444(7121):860-7 - PubMed
  19. BMC Immunol. 2011 Feb 28;12:18 - PubMed
  20. Mol Cell Biochem. 2011 Aug;354(1-2):207-17 - PubMed
  21. J Exp Med. 2011 Apr 11;208(4):715-27 - PubMed
  22. Mol Cells. 2006 Apr 30;21(2):174-85 - PubMed
  23. Diabetologia. 2005 Nov;48(11):2282-91 - PubMed
  24. Gastroenterol Res Pract. 2010;2010:null - PubMed
  25. Diabetes. 2003 Apr;52(4):991-7 - PubMed
  26. Compr Physiol. 2013 Jul;3(3):1337-62 - PubMed
  27. Diabetes. 2009 Mar;58(3):579-89 - PubMed
  28. J Biol Chem. 2008 Apr 25;283(17):11107-16 - PubMed
  29. J Clin Invest. 2005 Aug;115(8):2083-98 - PubMed
  30. Am J Physiol Cell Physiol. 2013 Oct 15;305(8):C877-86 - PubMed
  31. Nat Rev Mol Cell Biol. 2008 Feb;9(2):162-76 - PubMed
  32. Curr Opin Endocrinol Diabetes Obes. 2011 Apr;18(2):139-43 - PubMed
  33. Curr Opin Clin Nutr Metab Care. 2013 Jul;16(4):418-24 - PubMed
  34. J Appl Physiol (1985). 2002 May;92(5):1789-94 - PubMed
  35. Nat Rev Immunol. 2004 Jul;4(7):499-511 - PubMed
  36. Curr Opin Immunol. 2000 Feb;12(1):20-6 - PubMed
  37. J Appl Physiol (1985). 2012 Oct;113(7):1082-90 - PubMed
  38. Prog Lipid Res. 2014 Jan;53:124-44 - PubMed
  39. Curr Diab Rep. 2005 Jun;5(3):167-70 - PubMed
  40. J Biol Chem. 2004 Apr 23;279(17):16971-9 - PubMed
  41. Diabetes Care. 2013 Mar;36(3):513-21 - PubMed
  42. Am J Physiol. 1996 Feb;270(2 Pt 1):E336-43 - PubMed
  43. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1526-30 - PubMed
  44. PLoS One. 2014 Apr 02;9(4):e93148 - PubMed
  45. Diabetes. 2000 Jun;49(6):992-8 - PubMed
  46. Cell. 2012 Mar 2;148(5):852-71 - PubMed
  47. Biochem Biophys Res Commun. 2002 Dec 20;299(5):853-6 - PubMed

Publication Types