Hostname: page-component-848d4c4894-pjpqr Total loading time: 0 Render date: 2024-06-28T01:15:49.050Z Has data issue: false hasContentIssue false
  • English
  • Français

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: mdonsmark@mfi.ku.dk
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

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

References

Abumrad, NA, Tepperman, HM & Tepperman, J (1980) Control of endogenous triglyceride breakdown in the mouse diaphragm. Journal of Lipid Research 21, 149–155.Google Scholar
Anthonsen, MW, Ronnstrand, L, Wernstedt, C, Degerman, E & Holm, C (1998) Identification of novel phosphorylation sites in hormone-sensitive lipase that are phosphorylated in response to isoproterenol and govern activation properties in vitro. Journal of Biological Chemistry 273, 215–221.Google Scholar
Carlson, LA, Ekelund, LG & Froberg, SO (1971) Concentration of triglycerides phospholipids and glycogen in skeletal muscle and of free fatty acids and beta-hydroxybutyric acid in blood in man in response to exercise. European Journal of Clinical Investigation 1, 248–254.Google Scholar
Donsmark, M, Langfort, J, Holm, C, Ploug, T & Galbo, H (2003) Contractions activate hormone-sensitive lipase in rat muscle by protein kinase C and mitogen-activated protein kinase. Journal of Physiology (London) 550, 845–854.Google Scholar
Enevoldsen, LH, Stallknecht, B, Fluckey, JD & Galbo, H (2000) Effect of exercise training on in vivo lipolysis in intra-abdominal adipose tissue in rats. American Journal of Physiology 279, E585–E592.Google Scholar
Enevoldsen, LH, Stallknecht, B, Langfort, J, Petersen, LN, Holm, C, Ploug, T & Galbo, H (2001) The effect of exercise training on hormone-sensitive lipase in rat intra-abdominal adipose tissue and muscle. Journal of Physiology (London) 536, 871–877.Google Scholar
Fredrikson, G, Tornqvist, H & Belfrage, P (1986) Hormone-sensitive lipase and monoacylglycerol lipase are both required for complete degradation of adipocyte triacylglycerol. Biochimica et Biophysica Acta 876, 288–293.Google Scholar
Galbo, H (1983) Hormonal and Metabolic Adaptations to Exercise Philadelphia PA: WB Saunders Company.Google Scholar
Garton, AJ, Campbell, DG, Carling, D, Hardie, DG, Colbran, RJ & Yeaman, SJ (1989) Phosphorylation of bovine hormone-sensitive lipase by the AMP-activated protein-kinase – A possible antilipolytic mechanism. European Journal of Biochemistry 179, 249–254.Google Scholar
Greenberg, AS, Shen, WJ, Muliro, K, Patel, S, Souza, SC, Roth, RA & Kraemer, FB (2001) Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signal-regulated kinase pathway. Journal of Biological Chemistry 276, 45456–45461.Google Scholar
Holm, C, Belfrage, P & Fredrikson, G (1987) Immunological evidence for the presence of hormone-sensitive lipase in rat-tissues other than adipose-tissue. Biochemical and Biophysical Research Communications 148, 99–105.Google Scholar
Holm, C, Kirchgessner, TG, Svenson, KL, Fredrikson, G, Nilsson, S, Miller, CG, Shively, JE, Heinzmann, C, Sparkes, RS, Mohandas, T, Lusis, AJ, Belfrage, P & Schotz, MC (1988) Hormone-sensitive lipase – Sequence expression, and chromosomal localization to 19 Cent-Q13.3. Science 241, 1503–1506.Google Scholar
Holm, C Østerlund, T (1998) Hormone-sensitive lipase and cholesteryl esterlipase Methods In Molecular Biology: Lipases and Phospholipases Protocols, pp. 109–121 [Doolittle, MH, Reue, K, editors]. Totowa, NJ: Human Press Inc.Google Scholar
Holm, C Østerlund, T, Laurell, H & Contreras, JA (2000) Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Annual Review of Nutrition 20, 365–393.Google Scholar
Hopp, JF & Palmer, WK (1990) Effect of electrical-stimulation on intracellular triacylglycerol in isolated skeletal-muscle. Journal of Applied Physiology 68, 348–354.Google Scholar
Hurley, BF, Nemeth, PM, Martin, WH, Hagberg, JM, Dalsky, GP & Holloszy, JO (1986) Muscle triglyceride utilization during exercise – Effect of training. Journal of Applied Physiology 60, 562–567.Google Scholar
Langfort, J, Ploug, T, Donsmark, M, Gorski, J & Galbo, H (2002) Training enhances contraction-mediated hormone-sensitive lipase activation in rat soleus muscleIn 7th Annual Congress of the European College of Sports Science, 24–28 July, Athens,p.1137[Koskolou, M, Geladas, N, and Klissouras, V, editors]. Athens, Greece: Pashalidis Medical Publisher.Google Scholar
Langfort, J, Ploug, T, Ihlemann, J, Baranczuk, E, Donsmark, M, Gorski, J & Galbo, H (2003) Additivity of adrenaline and contractions on hormone-sensitive lipase, but not on glycogen phosphorylase, in rat muscle. Acta Physiologica Scandinavica 178, 51–60.Google Scholar
Langfort, J, Ploug, T, Ihlemann, J, Holm, C & Galbo, H (2000) Stimulation of hormone-sensitive lipase activity by contractions in rat skeletal muscle. Biochemical Journal 351, 207–214.Google Scholar
Langfort, J, Ploug, T, Ihlemann, J, Saldo, M, Holm, C & Galbo, H (1999) Expression of hormone-sensitive lipase and its regulation by adrenaline in skeletal muscle. Biochemical Journal 340, 459–465.Google Scholar
Langin, D, Holm, C & Lafontan, M (1996) Adipocyte hormone-sensitive lipase: A major regulator of lipid metabolism. Proceedings of the Nutrition Society 55, 93–109.Google Scholar
Large, V, Arner, P, Reynisdottir, S, Grober, J, Van Harmelen, V, Holm, C & Langin, D (1998) Hormone-sensitive lipase expression and activity in relation to lipolysis in human fat cells. Journal of Lipid Research 39, 1688–1695.Google Scholar
Large, V, Reynisdottir, S, Langin, D, Fredby, K, Klannemark, M, Holm, C & Arner, P (1999) Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. Journal of Lipid Research 40, 2059–2066.Google Scholar
Martin, WH III (1996) Effects of acute and chronic exercise on fat metabolism. Exercise and Sport Sciences Reviews 24, 203–231.Google Scholar
Napoli, R, Gibson, L, Hirshman, MF, Boppart, MD, Dufresne, SD, Horton, ES & Goodyear, LJ (1998) Epinephrine and insulin stimulate different mitogen-activated protein kinase signaling pathways in rat skeletal muscle. Diabetes 47, 1549–1554.Google Scholar
Oscai, LB, Essig, DA & Palmer, WK (1990) Lipase regulation of muscle triglyceride hydrolysis. Journal of Applied Physiology 69, 1571–1577.Google Scholar
Phillips, SM, Green, HJ, Tarnopolsky, MA, Heigenhauser, GJ & Grant, SM (1996) Progressive effect of endurance training on metabolic adaptations in working skeletal muscle. American Journal of Physiology 270, E265–E272.Google Scholar
Reitman, J, Baldwin, KM & Holloszy, JO (1973) Intramuscular triglyceride utilization by red, white, and intermediate skeletal muscle and heart during exhausting exercise. Proceedings of the Society for Experimental Biology and Medicine 142, 628–631.Google Scholar
Small, CA, Garton, AJ & Yeaman, SJ (1989) The presence and role of hormone-sensitive lipase in heart-muscle. Biochemical Journal 258, 67–72.Google Scholar
Spriet, LL, Heigenhauser, GJ & Jones, NL (1986) Endogenous triacylglycerol utilization by rat skeletal-muscle during tetanic stimulation. Journal of Applied Physiology 60, 410–415.Google Scholar
Straalfors, P, Olsson, H & Belfrage, P (1987) Hormone-sensitive lipase. In The Enzymes, vol. 18,pp.147–177 [Boyer, PD, and Krebs, EG, editors]. New York: Academic Press Inc.Google Scholar
Su, CL, Sztalryd, C, Contreras, JA, Holm, C, Kimmel, AR & Londos, C (2003) Mutational analysis of the hormone-sensitive lipase translocation reaction in adipocytes. Journal of Biological Chemistry 278, 43615–43619.Google Scholar
Sztalryd, C & Kraemer, FB (1994) Regulation of hormone-sensitive lipase during fasting. American Journal of Physiology 266, E179–E185.Google Scholar
Van der Vusse, GJ & Reneman, RS (1996) Exercise: Regulation and Integration of Multiple Systems,pp. 952 – 994. Oxford: Oxford University Press.Google Scholar
Vaughan, M, Berger, JE & Steinberg, D (1964) Hormone-sensitive lipase and monoglyceride lipase activities in adipose tissue. Journal of Biological Chemistry 239, 401–409.Google Scholar
Widegren, U, Ryder, JW & Zierath, JR (2001) Mitogen-activated protein kinase signal transduction in skeletal muscle: effects of exercise and muscle contraction. Acta Physiologica Scandinavica 172, 227–238.Google Scholar
Yeaman, SJ (1990) Hormone-sensitive lipase – A multipurpose enzyme in lipid-metabolism. Biochimica et Biophysica Acta 1052, 128–132.Google Scholar