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Regulation and role of hormone-sensitive lipase in rat skeletal muscle

Published online by Cambridge University Press:  05 March 2007

Morten Donsmark ,
Jozef Langfort ,
Cecilia Holm ,
Thorkil Ploug  and
Henrik Galbo
Morten Donsmark*
Affiliation:
Copenhagen Muscle Research Centre, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark
Jozef Langfort
Affiliation:
Laboratory of Experimental Pharmacology, The Polish Academy of Sciences, Warsaw, Poland
Cecilia Holm
Affiliation:
Section for Molecular Signalling, Department of Cell and Molecular Biology, Lund University, Sweden
Thorkil Ploug
Affiliation:
Copenhagen Muscle Research Centre, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark
Henrik Galbo
Affiliation:
Copenhagen Muscle Research Centre, Department of Medical Physiology, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen N, Denmark Department of Rheumatology, Bispebjerg Hospital, Copenhagen, Denmark
*
*Corresponding author: Dr Morten Donsmark Fax: +45 35327555, Email: [email protected]
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Abstract

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Intramyocellular triacylglycerol (TG) is an important energy store, and the energy content of this depot is higher than the energy content of the muscle glycogen depot. It has recently been shown that the mobilization of fatty acids from this TG pool may be regulated by the neutral lipase hormone-sensitive lipase (HSL). This enzyme is known to be rate limiting for intracellular TG hydrolysis in adipose tissue. The presence of HSL has been demonstrated in all muscle fibre types by Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying. The content of HSL varies between fibre types, being higher in oxidative fibres than in glycolytic fibres. When analysed under conditions optimal for“ HSL, neutral lipase activity in muscle can be stimulated by adrenaline as well as by contractions. These increases are abolished by the presence of anti-HSL antibody during analysis. Moreover, immunoprecipitation with affinity-purified anti-HSL antibody causes similar reductions in muscle HSL protein concentration and in measured neutral lipase responses to contractions. The immunoreactive HSL in muscle is stimulated by adrenaline via β-adrenergic activation of cAMP-dependent protein kinase (PKA). From findings in adipocytes it is likely that PKA phosphorylates HSL at residues Ser563, Ser659and Ser660. Contraction probably also enhances muscle HSL activity by phosphorylation, because the contraction-induced increase in HSL activity is elevated by the protein phosphatase inhibitor okadaic acid and reversed by alkaline phosphatase. A novel signalling pathway in muscle by which HSL activity may be stimulated by protein kinase C (PKC) via extracellular signal-regulated kinase (ERK) has been demonstrated. In contrast to previous findings in adipocytes, in muscle the activation of ERK is not necessary for stimulation of HSL by adrenaline. However, contraction-induced HSL activation is mediated by PKC, at least partly via the ERK pathway. In fat cells ERK is known to phosphorylate HSL at Ser600. Hence, phosphorylation of different sites may explain the finding that in muscle the effects of contractions and adrenaline on HSL activity are partially additive. In line with the view that the two stimuli act by different mechanisms, training increases contraction-mediated HSL activation but diminishes adrenaline-mediated HSL activation in muscle. In conclusion, HSL is present in skeletal muscle and can be activated by phosphorylation in response to both adrenaline and muscle contractions. Training increases contraction-mediated HSL activation, but decreases adrenaline-mediated HSL activation in muscle.

Keywords

Hormone-sensitive lipaseAdrenalineExtracellular signal-regulated kinaseExerciseMuscle fibre types
Type
Symposium 4: New methodologies and insights in the regulation of fat metabolism during exercise
Information
Proceedings of the Nutrition Society , Volume 63 , Issue 2 , May 2004 , pp. 309 - 314
Copyright
Copyright © The Nutrition Society 2004

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