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J Cachexia Sarcopenia Muscle. 2012 Jun;3(2):117-37. doi: 10.1007/s13539-011-0047-1. Epub 2011 Nov 30.

The effect of exercise on IL-6-induced cachexia in the Apc ( Min/+) mouse.

Journal of cachexia, sarcopenia and muscle

Melissa J Puppa, James P White, Kandy T Velázquez, Kristen A Baltgalvis, Shuichi Sato, John W Baynes, James A Carson

Affiliations

  1. Integrative Muscle Biology Laboratory, Exercise Science Department, University of South Carolina, Columbia, SC, USA.

PMID: 22476915 PMCID: PMC3374019 DOI: 10.1007/s13539-011-0047-1

Abstract

BACKGROUND: Cachexia involves unintentional body weight loss including diminished muscle and adipose tissue mass and is associated with an underlying disease. Systemic overexpression of IL-6 accelerates cachexia in the Apc(Min/+) mouse, but does not induce wasting in control C57BL/6 mice. With many chronic diseases, chronic inflammation and metabolic dysfunction can be improved with moderate exercise. A direct effect of regular moderate exercise on the prevention of IL-6-induced cachexia in the Apc(Min/+) mouse has not been investigated. The purpose of this study was to assess the effects of exercise on the development of cachexia in the Apc(Min/+) mouse.

METHODS: Mice were randomly assigned to moderate treadmill exercise (18 m/min, 1 h, 6 days/week, 5% grade) or cage control (CC) groups from 6 to 14 weeks of age. At 12 weeks of age, mice were electroporated with either IL-6-containing or control plasmid into the quadriceps muscle. Mice were killed after 2 weeks of systemic IL-6 overexpression or control treatment.

RESULTS: IL-6 overexpression induced an 8% loss in body weight in CC mice, which was significantly attenuated by exercise. IL-6 overexpression in CC mice increased fasting insulin and triglyceride levels, which were normalized by exercise, and associated with increased oxidative capacity, an induction of AKT signaling, and a repression of AMPK signaling in muscle. These exercise-induced changes occurred despite elevated inflammatory signaling in skeletal muscle.

CONCLUSION: We conclude that moderate-intensity exercise can attenuate IL-6-dependent cachexia in Apc(Min/+) mice, independent of changes in IL-6 concentration and muscle inflammatory signaling. The exercise effect was associated with improved insulin sensitivity and improved energy status in the muscle.

References

  1. Diabetes Care. 2003 Mar;26(3):557-62 - PubMed
  2. J Appl Physiol (1985). 2001 Sep;91(3):1017-28 - PubMed
  3. Int J Cancer. 2010 Feb 1;126(3):756-63 - PubMed
  4. Cell Biochem Funct. 2008 Aug;26(6):701-8 - PubMed
  5. J Support Oncol. 2003 Sep-Oct;1(3):159-68 - PubMed
  6. Cancer Res. 1988 Dec 15;48(24 Pt 1):7079-81 - PubMed
  7. Cell Biochem Funct. 2000 Dec;18(4):249-58 - PubMed
  8. Cell Metab. 2006 Jul;4(1):75-87 - PubMed
  9. J Clin Endocrinol Metab. 2001 Jan;86(1):162-6 - PubMed
  10. Diabetologia. 2007 Feb;50(2):404-13 - PubMed
  11. Int J Cardiol. 2005 Apr 8;100(1):93-9 - PubMed
  12. Gut. 2006 Jan;55(1):62-7 - PubMed
  13. JAMA. 1999 May 12;281(18):1722-7 - PubMed
  14. Diabetes. 2002 Oct;51(10):2944-50 - PubMed
  15. Clin Cancer Res. 2007 Nov 1;13(21):6379-85 - PubMed
  16. Acta Oncol. 2007;46(1):118-20 - PubMed
  17. Eur J Endocrinol. 2003 Nov;149(5):421-4 - PubMed
  18. Am J Physiol Endocrinol Metab. 2008 Sep;295(3):E586-94 - PubMed
  19. Eur Respir J. 2009 May;33(5):1045-52 - PubMed
  20. Diabetes. 2006 Dec;55 Suppl 2:S48-54 - PubMed
  21. Curr Opin Clin Nutr Metab Care. 2005 May;8(3):265-9 - PubMed
  22. Scand J Med Sci Sports. 2007 Oct;17(5):580-7 - PubMed
  23. Eur Respir J. 2007 Jul;30(1):73-9 - PubMed
  24. Biochim Biophys Acta. 2011 Dec;1812(12):1601-6 - PubMed
  25. Am J Physiol. 1999 Dec;277(6):E1055-60 - PubMed
  26. J Nutr. 2005 Dec;135(12 Suppl):3002S-3008S - PubMed
  27. J Appl Physiol (1985). 1997 Jul;83(1):166-71 - PubMed
  28. Horm Metab Res. 1984 Nov;16(11):572-5 - PubMed
  29. J Clin Endocrinol Metab. 1997 Dec;82(12):4167-70 - PubMed
  30. J Cachexia Sarcopenia Muscle. 2010 Sep;1(1):7-8 - PubMed
  31. Cancer Res. 2007 Jun 1;67(11):5531-7 - PubMed
  32. Carcinogenesis. 2006 Oct;27(10):2103-7 - PubMed
  33. Biochem Biophys Res Commun. 2004 Jul 23;320(2):449-54 - PubMed
  34. Cancer Res. 1984 Dec;44(12 Pt 1):5910-3 - PubMed
  35. Cancer Prev Res (Phila). 2009 Jul;2(7):641-9 - PubMed
  36. Cancer Sci. 2008 Nov;99(11):2136-41 - PubMed
  37. Cancer Genomics Proteomics. 2010 Nov-Dec;7(6):287-302 - PubMed
  38. Cytokine. 2011 Aug;55(2):221-8 - PubMed
  39. J Biol Chem. 2008 Jan 11;283(2):708-15 - PubMed
  40. Physiol Rev. 2008 Oct;88(4):1379-406 - PubMed
  41. Clin Nutr. 2008 Dec;27(6):793-9 - PubMed
  42. Med Sci Monit. 2007 Sep;13(9):RA168-173 - PubMed
  43. Nutr Cancer. 2010;62(4):484-94 - PubMed
  44. Br J Surg. 1998 Dec;85(12):1658-62 - PubMed
  45. Growth Horm IGF Res. 2002 Dec;12(6):388-98 - PubMed
  46. PLoS One. 2011;6(9):e24650 - PubMed
  47. Science. 1990 Jan 19;247(4940):322-4 - PubMed
  48. J Clin Endocrinol Metab. 2011 Feb;96(2):494-503 - PubMed
  49. Diabetes. 2004 Apr;53(4):1060-7 - PubMed
  50. Oncologist. 2007;12 Suppl 1:52-67 - PubMed
  51. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):374-7 - PubMed
  52. Support Care Cancer. 2003 Feb;11(2):73-8 - PubMed
  53. Circulation. 2000 Oct 10;102(15):1847-53 - PubMed
  54. Int J Clin Oncol. 2009 Aug;14(4):315-20 - PubMed
  55. J Appl Physiol (1985). 2010 Apr;108(4):769-79 - PubMed
  56. Diabetes Care. 1997 Mar;20(3):385-91 - PubMed
  57. Cell. 2004 Apr 30;117(3):399-412 - PubMed
  58. Horm Metab Res. 2003 Jun;35(6):337-42 - PubMed
  59. J Appl Physiol (1985). 2010 Oct;109(4):1155-61 - PubMed
  60. Eur Cytokine Netw. 2004 Oct-Dec;15(4):312-6 - PubMed
  61. J Clin Invest. 1992 May;89(5):1681-4 - PubMed
  62. J Appl Physiol (1985). 2005 Jun;98(6):2219-25 - PubMed
  63. J Appl Physiol (1985). 2008 Apr;104(4):1137-43 - PubMed
  64. Exerc Sport Sci Rev. 2010 Oct;38(4):168-76 - PubMed
  65. Diabetes. 2006 Dec;55 Suppl 2:S9-S15 - PubMed
  66. Curr Opin Clin Nutr Metab Care. 2003 Jan;6(1):87-93 - PubMed
  67. Biochem J. 2003 Aug 15;374(Pt 1):1-20 - PubMed
  68. Mediators Inflamm. 2008;2008:109502 - PubMed
  69. J Clin Endocrinol Metab. 2003 Jul;88(7):3005-10 - PubMed
  70. Int J Sports Med. 2000 Jan;21(1):21-4 - PubMed
  71. Circulation. 2008 Jul 22;118(4):346-54 - PubMed
  72. Am J Clin Nutr. 2009 Jan;89(1):467S-71S - PubMed
  73. Am J Physiol Regul Integr Comp Physiol. 2011 Feb;300(2):R201-11 - PubMed
  74. Diabetes Care. 2001 Feb;24(2):362-5 - PubMed
  75. Amino Acids. 2012 May;42(5):1783-92 - PubMed
  76. Pflugers Arch. 2009 Mar;457(5):989-1001 - PubMed
  77. Acta Diabetol. 2013 Apr;50(2):189-200 - PubMed
  78. Science. 2011 Jul 8;333(6039):233-8 - PubMed
  79. J Appl Physiol Respir Environ Exerc Physiol. 1983 Dec;55(6):1660-4 - PubMed
  80. Support Care Cancer. 2010 Dec;18(12):1539-44 - PubMed
  81. Am J Physiol Regul Integr Comp Physiol. 2008 Feb;294(2):R393-401 - PubMed
  82. J Appl Physiol Respir Environ Exerc Physiol. 1984 May;56(5):1217-22 - PubMed
  83. Endocr J. 2006 Apr;53(2):189-95 - PubMed
  84. JAMA. 2001 Jul 18;286(3):327-34 - PubMed
  85. J Investig Med. 2010 Mar;58(3):554-9 - PubMed

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