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Aerobic training reverses high-fat diet-induced pro-inflammatory signalling in rat skeletal muscle

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Abstract

High-fat feeding activates components of the pro-inflammatory pathway and increases co-immunoprecipitation of suppressor of cytokine signalling (SOCS)-3 with both the insulin receptor (IR)-β subunit and IRS-1, which together contribute to keeping PI-3 kinase from being fully activated. However, whether aerobic training reverses these impairments is unknown. Sprague-Dawley rats were fed a chow (CON, n = 8) or saturated high-fat (n = 16) diets for 4 weeks. High-fat-fed rats were then allocated (n = 8/group) to either sedentary (HF) or aerobic exercise training (HFX) for an additional 4 weeks after which all animals underwent hind limb perfusions. Insulin-stimulated red quadriceps 3-O-methylglucose transport rates and PI-3 kinase activity were greater (p < 0.05) in CON and HFX compared to HF. IRS-1 tyrosine phosphorylation was increased (p < 0.05) and IRS-1 serine 307 phosphorylation was decreased (p < 0.05) in HFX compared to HF. IR-β subunit co-immunoprecipitation with IRS-1 was increased in HFX compared to HF. SOCS-3 co-immunoprecipitation with both the IR-β subunit and IRS-1 was decreased (p < 0.05) in HFX compared to HF. IKKα/β serine phosphorylation, and IκBα serine phosphorylation were decreased (p < 0.05) while IκBα protein concentration was increased in HFX compared to HF. By decreasing the association of SOCS-3 with both the IR-β subunit and IRS-1 the interaction between IRS-1 and the IR-β subunit was normalized in the HFX, and may have contributed to skeletal muscle PI-3 kinase being fully activated by insulin. Additionally, the reduction in IKKα/β serine phosphorylation in HFX may have contributed to decreasing IRS-1 serine phosphorylation, and in turn, promoted the normalization of insulin-stimulated activation of PI-3 kinase.

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Acknowledgments

This study was supported by grants from the National Institutes of Health (GM-48680, GM-08395 and DK-57625).

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Correspondence to Ben B. Yaspelkis III.

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Communicated by Martin Flueck.

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Yaspelkis III, B.B., Kvasha, I.A., Lessard, S.J. et al. Aerobic training reverses high-fat diet-induced pro-inflammatory signalling in rat skeletal muscle. Eur J Appl Physiol 110, 779–788 (2010). https://doi.org/10.1007/s00421-010-1559-7

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