Contraction‐induced lipolysis is not impaired by inhibition of hormone‐sensitive lipase in skeletal muscle. (16th August 2013)

• Record Type: Journal Article
• Authors: Alsted, Thomas J.; Ploug, Thorkil; Prats, Clara; Serup, Annette K.; Høeg, Louise; Schjerling, Peter; Holm, Cecilia; Zimmermann, Robert; Fledelius, Christian; Galbo, Henrik; Kiens, Bente
• Is Part Of: Journal of physiology. Volume 591:Number 20(2013:Oct.)
• Page Start: 5141
• Page End: 5155
• Publication Date: 2013-08-16
• Subjects: Physiology -- Periodicals; 612.005
• DOI: 10.1113/jphysiol.2013.260794
• Languages: English
• ISSNs: 0022-3751

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Key points</title> <p> <list id="l1" list-type="simple"> <list-item> <label> </label> <p>In skeletal muscle hormone‐sensitive lipase (HSL) is considered the only enzyme responsible for breakdown of intramyocellular triacylglycerol (IMTG) during contractions. This notion is based on indirect measures in which important cellular events are not taken into account.</p> </list-item> <list-item> <label> </label> <p>Using two histochemical techniques to measure breakdown of IMTG during contractions in isolated skeletal muscles we found that IMTG was decreased (1) in rat muscles during acute pharmacological blockade of HSL, and (2) in muscles of HSL knockout mice.</p> </list-item> <list-item> <label> </label> <p>We demonstrated that adipose triglyceride lipase (ATGL) and HSL collectively account for at least 98% of the total TG lipase activity in mouse muscle, and other TG lipases accordingly seem of negligible importance for breakdown of IMTG.</p> </list-item> <list-item> <label> </label> <p>In conclusion, breakdown of IMTG occurs in the contracting muscle in the absence of HSL activity. Our data suggest that ATGL is activated during contractions and plays a major role in breakdown of IMTG.</p> </list-item> </list> </p> <p> <bold>Abstract </bold> 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 <italic>in vitro</italic> lipase activity data, which may not reflect the <italic>in vivo</italic> lipolytic activity. We investigated lipolysis of IMTG in soleus muscles electrically stimulated to contract <italic>ex vivo</italic> 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 (<italic>P</italic> < 0.001). In response to contractions IMTG staining decreased significantly in both HSL‐KO and WT muscles (<italic>P</italic> < 0.05). <italic>In vitro</italic> 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.</p> </abstract>