Exercise normalises overexpression of TNF-α in knockout mice

TNF-α is linked with insulin resistance, as greater amounts of TNF are detected in muscle and adipose tissue in glycemically challenged people and TNF-α inhibits insulin receptor signalling. However, what modulates this overexpression of TNF-α is currently unknown. We examined the effect of 1h exercise on overexpression of the TNF-α 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-α in response to exercise. TNF-α gene expression was over-expressed in muscle in both TNFR knockout models. TNF-α overexpression returned to normal levels after exercise in the TNF-α receptor knockout models. In IL-6 knockout mice, a modest decrease in TNF-α was also observed. These data suggest that TNF-α-induced insulin resistance can be regulated by a single exercise bout by normalising TNF-α expression. This exercise effect can be mediated via IL-6, but also an IL-6 independent mechanism seems to exist. © 2004 Published by Elsevier Inc.