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Exercise normalises overexpression of TNF-alpha in knockout mice

Charlotte Keller, Pernille Keller, Mercé Giralt, Juan Hidalgo, Bente Klarlund Pedersen

95 Citations (Scopus)

Abstract

TNF-alpha is linked with insulin resistance, as greater amounts of TNF are detected in muscle and adipose tissue in glycemically challenged people and TNF-alpha inhibits insulin receptor signalling. However, what modulates this overexpression of TNF-alpha is currently unknown. We examined the effect of 1 h exercise on overexpression of the TNF-alpha gene in TNF receptor 1 and 2 knockout mice. IL-6 knockout mice were included to elucidate the importance of IL-6 in regulating TNF-alpha in response to exercise. TNF-alpha gene expression was over-expressed in muscle in both TNFR knockout models. TNF-alpha overexpression returned to normal levels after exercise in the TNF-alpha receptor knockout models. In IL-6 knockout mice, a modest decrease in TNF-alpha was also observed. These data suggest that TNF-alpha-induced insulin resistance can be regulated by a single exercise bout by normalising TNF-alpha expression. This exercise effect can be mediated via IL-6, but also an IL-6 independent mechanism seems to exist.

Original languageEnglish
JournalBiochemical and Biophysical Research Communications
Volume321
Issue number1
Pages (from-to)179-82
Number of pages4
ISSN0006-291X
DOIs
Publication statusPublished - 13 Aug 2004
Externally publishedYes

Keywords

  • Adipose Tissue/physiology
  • Animals
  • Antigens, CD/genetics
  • Female
  • Insulin Resistance/genetics
  • Interleukin-6/deficiency
  • Male
  • Mice
  • Mice, Knockout
  • Muscle, Skeletal/physiology
  • Physical Conditioning, Animal/physiology
  • RNA, Messenger/genetics
  • Receptors, Tumor Necrosis Factor/deficiency
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha/genetics

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