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Resistance exercise, but not endurance exercise, induces IKKβ phosphorylation in human skeletal muscle of training-accustomed individuals

  • Muscle physiology
  • Published:
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Abstract

The mammalian target of rapamycin complex 1 (mTORC1) is considered an important role in the muscular adaptations to exercise. It has been proposed that exercise-induced signaling to mTORC1 do not require classic growth factor PI3K/Akt signaling. Activation of IKKβ and the mitogen-activated protein kinases (MAPKs) Erk1/2 and p38 has been suggested to link inflammation and cellular stress to activation of mTORC1 through the tuberous sclerosis 1 (TSC1)/tuberous sclerosis 2 (TSC2) complex. Consequently, activation of these proteins constitutes potential alternative mechanisms of mTORC1 activation following exercise. Previously, we demonstrated that mTOR is preferentially activated in response to resistance exercise compared to endurance exercise in trained individuals without concomitant activation of Akt. In the present study, we extended this investigation by examining IκB kinase complex (IKK), TSC1, MAPK, and upstream Akt activators, along with gene expression of selected cytokines, in skeletal muscles from these subjects. Biopsies were sampled prior to, immediately after, and in the recovery period following resistance exercise, endurance exercise, and control interventions. The major finding was that IKKβ phosphorylation increased exclusively after resistance exercise. No changes in TSC1, Erk1/2, insulin receptor, or insulin receptor substrate 1 phosphorylation were observed in any of the groups, while p38 phosphorylation was higher in the resistance exercise group compared to both other groups immediately after the intervention. Resistance and endurance exercise increased IL6, IL8, and TNFα gene expression immediately after exercise. The non-exercise control group demonstrated that cytokine gene expression is also sensitive to repeated biopsy sampling, whereas no effect of repeated biopsy sampling on protein expression and phosphorylation was observed. In conclusion, resistance exercise, but not endurance exercise, increases IKKβ phosphorylation in trained human subjects, which support the idea that IKKβ can influence the activation of mTORC1 in human skeletal muscle.

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Acknowledgments

Tue Kjølhede, Jean Farup, and Poul F. Vestergaard from the Section of Sport Science, Department of Public Health, Aarhus University, Denmark, is thanked for their contribution as training supervisors throughout the training period and for their contribution to the completion of the single-bout experiment. Anja Jokipii is acknowledged for skilled technical assistance with the mRNA analysis.

Grants

Niels Jessen was supported by the Danish Agency for Science Technology and Innovation (grant 271-07-0719). Kristian Vissing was supported by the Novo Nordisk Foundation. Peter Schjerling was supported by The Danish Medical Research Council and Nordea Foundation (Healthy Ageing grant).

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Authors and Affiliations

  1. Research Laboratory for Biochemical Pathology, Institute of Clinical Medicine, Aarhus University Hospital, Nørrebrogade 44, 8000, Aarhus, Denmark

    Andreas Buch Møller, Berthil Forrest Clasen & Niels Jessen

  2. Department of Internal Medicine and Endocrinology, Aarhus University Hospital, Aarhus, Denmark

    Mikkel Holm Vendelbo & Niels Jessen

  3. Section of Sport Science, Department of Public Health, Aarhus University, Aarhus, Denmark

    Stine Klejs Rahbek & Kristian Vissing

  4. Institute of Sports Medicine, Department of Orthopaedic Surgery M, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Peter Schjerling

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  1. Andreas Buch Møller
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Correspondence to Niels Jessen.

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Møller, A.B., Vendelbo, M.H., Rahbek, S.K. et al. Resistance exercise, but not endurance exercise, induces IKKβ phosphorylation in human skeletal muscle of training-accustomed individuals. Pflugers Arch - Eur J Physiol 465, 1785–1795 (2013). https://doi.org/10.1007/s00424-013-1318-9

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