title: Exercise normalises overexpression of TNF-alpha in knockout mice.
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.
authors.affiliation: Copenhagen Muscle Research Centre, Rigshospitalet, Denmark. charlotte_keller@yahoo.com
authors.forename: Charlotte
authors.initials: C
authors.lastname: Keller
authors.forename: Pernille
authors.initials: P
authors.lastname: Keller
authors.forename: Mercé
authors.initials: M
authors.lastname: Giralt
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
authors.forename: Bente Klarlund
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D005260:Female; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D015703:Antigens, CD; D015850:Interleukin-6; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha