Pflügers Archiv - European Journal of Physiology

, Volume 470, Issue 11, pp 1597–1613 | Cite as

Impact of skeletal muscle IL-6 on regulation of liver and adipose tissue metabolism during fasting

  • Lærke Bertholdt
  • Anders Gudiksen
  • Henrik Jessen
  • Henriette PilegaardEmail author
Integrative Physiology
Part of the following topical collections:
  1. Integrative Physiology


The liver and adipose tissue are important tissues in whole-body metabolic regulation during fasting. Interleukin 6 (IL-6) is a cytokine shown to be secreted from contracting muscle in humans and suggested to signal to the liver and adipose tissue. Furthermore, skeletal muscle IL-6 has been proposed to play a role during fasting. Therefore the aim of the present study was to investigate the role of skeletal muscle IL-6 in the regulation of substrate production in the liver and adipose tissue during fasting. Male skeletal muscle-specific IL-6 knockout (IL-6 MKO) mice and littermate floxed (control) mice fasted for 6 or 18 h (6 h fasting or 18 h fasting) with corresponding fed control groups (6 h fed or 18 h fed) and liver and adipose tissue were quickly obtained. Plasma β-hydroxybutyrate increased and hepatic glucose, lactate and glycogen decreased with fasting. In addition, fasting increased phosphoenolpyruvate carboxykinase protein and phosphorylation of pyruvate dehydrogenase (PDH) in the liver as well as hormone-sensitive lipase (HSL)Ser660 and HSLSer563 phosphorylation, PDH phosphorylation, adipose triglyceride lipase phosphorylation and perilipin phosphorylation and protein content in adipose tissue without any effect of lack of skeletal muscle IL-6. In conclusion, fasting induced regulation of enzymes in adipose tissue lipolysis and glyceroneogenesis as well as regulation of hepatic gluconeogenic capacity and hepatic substrate utilization in mice. However, skeletal muscle IL-6 was not required for these fasting-induced effects, but had minor effects on markers of lipolysis and glyceroneogenesis in adipose tissue as well as markers of hepatic gluconeogenesis in the fed state.


Skeletal muscle IL-6 Fasting Adipose tissue lipolysis Hepatic glucose production Substrate regulation 



The authors would like to thank Stine Ringholm for technical assistance and Professor Grahame Hardie (University of Dundee) for providing antibodies as well as Professor Juan Hidalgo (Universidad de Autonoma de Barcelona) for initially providing floxed IL-6 mice to start breeding.


This study was funded by Danish Council for Independent Research, Natural Sciences (4004-00134) and The Danish Diabetes Academy (1105701001).

Compliance with ethical standards


The authors have nothing to disclose.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Lærke Bertholdt
    • 1
  • Anders Gudiksen
    • 1
  • Henrik Jessen
    • 1
  • Henriette Pilegaard
    • 1
    Email author
  1. 1.Section for Cell Biology and Physiology, Department of BiologyUniversity of CopenhagenCopenhagenDenmark

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