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

Alsted, Thomas J. ; Ploug, Thorkil ; Prats, Clara ; Serup, Annette K. ; Hoeg, Louise ; Schjerling, Peter ; Holm, Cecilia LU ; Zimmermann, Robert ; Fledelius, Christian and Galbo, Henrik , et al. (2013) In Journal of Physiology 591(20). p.5141-5155
Abstract
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Physiology
volume
591
issue
20
pages
5141 - 5155
publisher
The Physiological Society
external identifiers
  • wos:000325980700023
  • scopus:84885413243
  • pmid:23878361
ISSN
1469-7793
DOI
10.1113/jphysiol.2013.260794
language
English
LU publication?
yes
id
6115fb80-36b7-4187-8852-7c5dc3d4e479 (old id 4158086)
date added to LUP
2016-04-01 13:05:43
date last changed
2022-04-13 23:13:01
@article{6115fb80-36b7-4187-8852-7c5dc3d4e479,
  abstract     = {{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 &lt; 0.001). In response to contractions IMTG staining decreased significantly in both HSL-KO and WT muscles (P &lt; 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.}},
  author       = {{Alsted, Thomas J. and Ploug, Thorkil and Prats, Clara and Serup, Annette K. and Hoeg, Louise and Schjerling, Peter and Holm, Cecilia and Zimmermann, Robert and Fledelius, Christian and Galbo, Henrik and Kiens, Bente}},
  issn         = {{1469-7793}},
  language     = {{eng}},
  number       = {{20}},
  pages        = {{5141--5155}},
  publisher    = {{The Physiological Society}},
  series       = {{Journal of Physiology}},
  title        = {{Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle}},
  url          = {{http://dx.doi.org/10.1113/jphysiol.2013.260794}},
  doi          = {{10.1113/jphysiol.2013.260794}},
  volume       = {{591}},
  year         = {{2013}},
}