Importance of an appropriate stress response for the metabolic and functional adaptations to exercise: Is Interleukin-6 the mediator?
Final Report Abstract
Interleukin (IL)-6 is a stress-inducible cytokine, which is also expressed and released from the contracting muscle during exercise. We set out to elucidate the function of IL-6 as potential mediator of the beneficial effects of exercise on glucose tolerance and oxidative metabolism. We established acute and chronic exercise protocols for wildtype and IL-6-/-mice, we studied the effect of an intramuscular application of IL-6 mRNA in wildtype mice, and we investigated the differentiation of primary IL-6-/- myoblasts. The overall conclusion from our studies is that IL-6 has defined metabolic effects in vitro and in vivo and affects myoblast fusion. It is not the essential exercise factor that is crucial for improvements in exercise capacity, oxidative metabolism and glucose tolerance by physiological, moderate training. The functional importance of IL-6 may become evident following muscle overload when a substantial increase in systemic IL-6 levels is found. Here, the observed effects of IL-6 on gene expression, glucose production or myoblast fusion could be part of stress defense mechanisms. In further studies we identified the liver as an important target organ of moderate intense exercise which was shown as energy depletion, strong activation of stress responsive pathways and a pronounced transcriptional response. Increased hepatic lipid storage in the recovery phase was shown by lipidomics analysis.
Publications
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Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise. Diabetologia. 53:1131-1141, 2010
Hoene M, Franken H, Fritsche L, Lehmann R, Pohl AK, Häring HU, Zell A,Schleicher ED, Weigert C
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IL-6 deficiency in mice neither impairs induction of metabolic genes in the liver nor affects blood glucose levels during fasting and moderately intense exercise. Diabetologia. 53:1732-1742, 2010
Fritsche L, Hoene M, Lehmann R, Ellingsgaard H, Hennige AM, Pohl AK, Häring HU, Schleicher ED, Weigert C
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Lipidomics analysis reveals efficient storage of hepatic triacylglycerides enriched in unsaturated fatty acids after one bout of exercise in mice. PLoS One. 5(10):e13318, 2010
Hu C, Hoene M, Zhao X, Häring HU, Schleicher E, Lehmann R, Han X, Xu G, Weigert C
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The stress response of the liver to physical exercise. Exerc Immunol Rev.16:163-83, 2010
Hoene M, Weigert C
