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Nutr Metab (Lond). 2012 Dec 05;9(1):109. doi: 10.1186/1743-7075-9-109.

Leptin differentially regulate STAT3 activation in ob/ob mouse adipose mesenchymal stem cells.

Nutrition & metabolism

Zhou Zhou, Manish Neupane, Hui Ren Zhou, Dayong Wu, Chia-Cheng Chang, Naima Moustaid-Moussa, Kate J Claycombe

Affiliations

  1. Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan, MI 48824, USA. [email protected].

PMID: 23216800 PMCID: PMC3559810 DOI: 10.1186/1743-7075-9-109

Abstract

BACKGROUND: Leptin-deficient ob/ob mice exhibit adipocyte hypertrophy and hyperplasia as well as elevated adipose tissue and systemic inflammation. Multipotent stem cells isolated from adult adipose tissue can differentiate into adipocytes ex vivo and thereby contribute toward increased adipocyte cell numbers, obesity, and inflamm ation. Currently, information is lacking regarding regulation of adipose stem cell numbers as well as leptin-induced inflammation and its signaling pathway in ob/ob mice.

METHODS: Using leptin deficient ob/ob mice, we investigated whether leptin injection into ob/ob mice increases adipose stem cell numbers and adipose tissue inflammatory marker MCP-1 mRNA and secretion levels. We also determined leptin mediated signaling pathways in the adipose stem cells.

RESULTS: We report here that adipose stem cell number is significantly increased following leptin injection in ob/ob mice and with treatment of isolated stem cells with leptin in vitro. Leptin also up-regulated MCP-1 secretion in a dose- and time-dependent manner. We further showed that increased MCP-1 mRNA levels were due to increased phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) Ser727 but not STAT3 Tyr705 phosphorylation, suggesting differential regulation of MCP-1 gene expression under basal and leptin-stimulated conditions in adipose stem cells.

CONCLUSIONS: Taken together, these studies demonstrate that leptin increases adipose stem cell number and differentially activates STAT3 protein resulting in up-regulation of MCP-1 gene expression. Further studies of mechanisms mediating adipose stem cell hyperplasia and leptin signaling in obesity are warranted and may help identify novel anti-obesity target strategies.

References

  1. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14564-8 - PubMed
  2. Growth Dev Aging. 1996 Autumn-Winter;60(3-4):145-51 - PubMed
  3. Eur J Immunol. 2007 Aug;37(8):2337-48 - PubMed
  4. J Clin Invest. 2003 Dec;112(12):1821-30 - PubMed
  5. FEBS Lett. 1997 Feb 10;403(1):79-82 - PubMed
  6. J Endocrinol. 2006 Sep;190(3):659-67 - PubMed
  7. Biochem J. 2002 Jun 15;364(Pt 3):875-9 - PubMed
  8. Obesity (Silver Spring). 2011 Mar;19(3):581-7 - PubMed
  9. J Allergy Clin Immunol. 2005 Dec;116(6):1228-34 - PubMed
  10. JAMA. 2003 Apr 9;289(14):1799-804 - PubMed
  11. Cell Immunol. 2001 Jul 10;211(1):30-6 - PubMed
  12. Am J Physiol. 1980 Oct;239(4):E265-E268 - PubMed
  13. J Immunol. 2005 Jun 1;174(11):6820-8 - PubMed
  14. Diabetes. 2004 May;53(5):1285-92 - PubMed
  15. Nature. 1998 Aug 27;394(6696):897-901 - PubMed
  16. J Biol Chem. 2009 Nov 6;284(45):31142-55 - PubMed
  17. Biochem Biophys Res Commun. 2004 Apr 30;317(2):598-604 - PubMed
  18. J Immunol. 2007 Jul 15;179(2):1292-302 - PubMed
  19. Stem Cells. 2010 Jun;28(6):1071-80 - PubMed
  20. Am J Physiol Endocrinol Metab. 2007 Nov;293(5):E1153-8 - PubMed
  21. J Immunol. 2002 Jan 15;168(2):875-82 - PubMed
  22. Eur J Endocrinol. 2003 May;148(5):535-42 - PubMed
  23. J Biol Chem. 2001 Nov 9;276(45):42534-42 - PubMed
  24. Int J Obes Relat Metab Disord. 2003 Aug;27(8):889-95 - PubMed
  25. FASEB J. 1998 Jan;12(1):57-65 - PubMed
  26. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2017-21 - PubMed
  27. Antioxid Redox Signal. 2007 Oct;9(10):1581-90 - PubMed
  28. Am J Physiol Cell Physiol. 2002 Apr;282(4):C853-63 - PubMed
  29. J Biol Chem. 2008 Jun 27;283(26):18238-47 - PubMed
  30. Am J Physiol Endocrinol Metab. 2010 May;298(5):E930-40 - PubMed
  31. Mol Cell Biol Res Commun. 2000 Sep;4(3):144-50 - PubMed
  32. Clin Exp Immunol. 2005 Oct;142(1):31-8 - PubMed
  33. Metabolism. 1998 Jul;47(7):844-7 - PubMed
  34. J Biol Chem. 2000 Apr 14;275(15):11348-54 - PubMed
  35. J Clin Invest. 2005 May;115(5):1111-9 - PubMed
  36. Cell. 2008 Oct 17;135(2):240-9 - PubMed
  37. Eur Cytokine Netw. 2000 Mar;11(1):7-14 - PubMed
  38. Basic Res Cardiol. 2003 Feb;98(1):33-8 - PubMed
  39. J Clin Endocrinol Metab. 2001 Feb;86(2):783-91 - PubMed
  40. Endocrinology. 2005 Aug;146(8):3334-42 - PubMed
  41. Mediators Inflamm. 2010;2010: - PubMed
  42. Endocrinology. 2004 Jul;145(7):3258-64 - PubMed
  43. J Clin Invest. 2003 Dec;112(12):1796-808 - PubMed

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