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Cecilia Holm

Professor

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Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle

Author

  • Thomas J. Alsted
  • Thorkil Ploug
  • Clara Prats
  • Annette K. Serup
  • Louise Hoeg
  • Peter Schjerling
  • Cecilia Holm
  • Robert Zimmermann
  • Christian Fledelius
  • Henrik Galbo
  • Bente Kiens

Summary, in English

In skeletal muscle hormone-sensitive lipase (HSL) has long been accepted to be the principal enzyme responsible for lipolysis of intramyocellular triacylglycerol (IMTG) during contractions. However, this notion is based on in vitro lipase activity data, which may not reflect the in vivo lipolytic activity. We investigated lipolysis of IMTG in soleus muscles electrically stimulated to contract ex vivo during acute pharmacological inhibition of HSL in rat muscles and in muscles from HSL knockout (HSL-KO) mice. Measurements of IMTG are complicated by the presence of adipocytes located between the muscle fibres. To circumvent the problem with this contamination we analysed intramyocellular lipid droplet content histochemically. At maximal inhibition of HSL in rat muscles, contraction-induced breakdown of IMTG was identical to that seen in control muscles (P < 0.001). In response to contractions IMTG staining decreased significantly in both HSL-KO and WT muscles (P < 0.05). In vitro TG hydrolase activity data revealed that adipose triglyceride lipase (ATGL) and HSL collectively account for approximate to 98% of the TG hydrolase activity in mouse skeletal muscle, other TG lipases accordingly being of negligible importance for lipolysis of IMTG. The present study is the first to demonstrate that contraction-induced lipolysis of IMTG occurs in the absence of HSL activity in rat and mouse skeletal muscle. Furthermore, the results suggest that ATGL is activated and plays a major role in lipolysis of IMTG during muscle contractions.

Department/s

  • Molecular Endocrinology
  • EXODIAB: Excellence in Diabetes Research in Sweden

Publishing year

2013

Language

English

Pages

5141-5155

Publication/Series

Journal of Physiology

Volume

591

Issue

20

Document type

Journal article

Publisher

The Physiological Society

Topic

  • Physiology

Status

Published

Research group

  • Molecular Endocrinology

ISBN/ISSN/Other

  • ISSN: 1469-7793