title: Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle.
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 < 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 ∼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.
authors.affiliation: B. Kiens: Section of Molecular Physiology, Department of Nutrition, Exercise and Sport, University of Copenhagen, Universitetsparken 13, DK, 2100 Copenhagen, Denmark. bkiens@ifi.ku.dk.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Alsted
authors.forename: Thorkil
authors.initials: T
authors.lastname: Ploug
authors.forename: Clara
authors.initials: C
authors.lastname: Prats
authors.forename: Annette K
authors.initials: AK
authors.lastname: Serup
authors.forename: Louise
authors.initials: L
authors.lastname: Høeg
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.forename: Cecilia
authors.initials: C
authors.lastname: Holm
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Christian
authors.initials: C
authors.lastname: Fledelius
authors.forename: Henrik
authors.initials: H
authors.lastname: Galbo
authors.forename: Bente
authors.initials: B
authors.lastname: Kiens
mesh_terms: D000818:Animals; D008049:Lipase / Q000378:metabolism; D008066:Lipolysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D002787:Sterol Esterase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
chemical_list: D014280:Triglycerides; D002787:Sterol Esterase; D008049:Lipase