Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-23T00:16:54.187Z Has data issue: false hasContentIssue false
  • English
  • Français

Regulation and role of hormone-sensitive lipase activity in human skeletal muscle

Published online by Cambridge University Press:  05 March 2007

Matthew J. Watt  and
Lawrence L. Spriet
Matthew J. Watt
Affiliation:
Department of Human Biology & Nutritional Sciences, University of Guelph, Ontario, Canada School of Medical Sciences, RMIT University, Bundoora, Victoria, Australia
Lawrence L. Spriet*
Affiliation:
Department of Human Biology & Nutritional Sciences, University of Guelph, Ontario, Canada
*
*Corresponding author: Dr Lawrence L. Spriet Fax: +1 1519 763 5902, Email: [email protected]
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.

Hormone-sensitive lipase (HSL) is believed to play a regulatory role in initiating the degradation of intramuscular triacylglycerol (IMTG) in skeletal muscle. A series of studies designed to characterise the response of HSL to three stimuli: exercise of varying intensities and durations; adrenaline infusions; altered fuel supply have recently been conducted in human skeletal muscle. In an attempt to understand the regulation of HSL activity the changes in the putative intramuscular and hormonal regulators of the enzyme have also been measured. In human skeletal muscle at rest there is a high constitutive level of HSL activity, which is not a function of biopsy freezing. The combination of low adrenaline and Ca2+levels and resting levels of insulin appear to dictate the level of HSL activity at rest. During the initial minute of low and moderate aerobic exercise HSL is activated by contractions in the apparent absence of increases in circulating adrenaline. During intense aerobic exercise, adrenaline may contribute to the early activation of HSL. The contraction-induced activation may be related to increased Ca2+and/or other unknown intramuscular activators. As low- and moderate-intensity exercise continues beyond a few minutes, activation by adrenaline through the cAMP cascade may also occur. With prolonged moderate-intensity exercise beyond 1–2 h and sustained high-intensity exercise, HSL activity decreases despite continuing increases in adrenaline, possibly as a result of increasing accumulations of free AMP, activation of AMP kinase and phosphorylation of inhibitory sites on HSL. The existing work in human skeletal muscle also suggests that there are numerous levels of control involved in the regulation of IMTG degradation, with control points downstream from HSL also being important. For example, it must be remembered that the actual flux (IMTG degradation) through HSL may be allosterically inhibited during prolonged exercise as a result of the accumulation of long-chain fatty acyl-CoA.

Keywords

Intramuscular triacylglycerolFat oxidationLipolysis
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. 315 - 322
Copyright
Copyright © The Nutrition Society 2004

References

Coyle, EF, Jeukendrup, AE, Oseto, MC, Hodgkinson, BJ & Zderic, TW (2001) Low-fat diet alters intramuscular substrates and reduces lipolysis and fat oxidation during exercise. American Journal of Physiology 280, E391–E398.Google Scholar
Coyle, EF, Jeukendrup, AE, Wagenmakers, AJ & Saris, WH (1998) Intramuscular triglyceride oxidation during exercise acutely increases with reduced plasma FFA mobilization and oxidation. FASEB Journal 10, A143.Google Scholar
Décombaz, J (2003) Nutrition and recovery of muscle energy stores after exercise. Sportmedizin und Sporttraumatologie 51, 31–38.Google Scholar
Décombaz, J, Schmitt, B, Ith, M, Decarli, B, Diem, P, Kreis, R, Hoppeler, H & Boesch, C (2001) Postexercise fat intake repletes intramyocellular lipids but no faster in trained than in sedentary subjects. American Journal of Physiology 281, R760–R769.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
Guo, Z, Burguera, B & Jensen, MD (2000) Kinetics of intramuscular triglyceride fatty acids in exercising humans. Journal of Applied Physiology 84, 1674–1679.Google Scholar
Holm, C, Osterlund, T, Laurell, H & Contreras, JA (2000) Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Annual Review of Nutrition 20, 365–393.Google Scholar
Howald, H, Boesch, C, Kreis, R, Matter, S, Billeter, R, Essen-Gustavsson, B & Hoppeler, H (2002) Content of intramyocellular lipids derived by electron microscopy, biochemical assays, and (1)H-MR spectroscopy. Journal of Applied Physiology 92, 2264–2272.CrossRefGoogle Scholar
Jepson, CA & Yeaman, SJ (1992) Inhibition of hormone-sensitive lipase by intermediary lipid metabolites. FEBS Letters 310, 197–200.Google Scholar
Kelley, DE, Goodpaster, BH & Storlien, L (2002) Muscle triglyceride and insulin resistance. Annual Reviews of Nutrition 22, 325–346.Google Scholar
Kiens, B, Essen-Gustavsson, B, Gad, P & Lithell, H (1987) Lipoprotein lipase activity and intramuscular triglyceride stores after long-term high-fat and high-carbohydrate diets in physically trained men. Clinical Physiology 7, 1–9.Google Scholar
Kjær, M, Howlett, K, Langfort, J, Zimmerman-Belsing, T, Lorentsen, J, Bulow, J, Ihlemann, J, Feldt-Rasmussen, U & Galbo, H (2000) Adrenaline and glycogenolysis in skeletal muscle during exercise: a study in adrenalectomised humans. Journal of Physiology 528, 371–378.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
Mottagui-Tabar, S, Ryden, M, Lofgren, P, Faulds, G, Hoffstedt, J, Brookes, AJ, Andersson, I & Arner, P (2003) Evidence for an important role of perilipin in the regulation of human adipoyte lipolysis. Diabetologia 46, 789–797.Google Scholar
Romijn, JA, Coyle, EF, Sidossis, LS, Gastaldelli, A, Horowitz, JF, Endert, E & Wolfe, RR (1993) Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. American Journal of Physiology 265, E380–E391.Google Scholar
Sacchetti, M, Saltin, B, Osada, T & Van Hall, G (2002) Intramuscular fatty acid metabolism in contracting and non-contracting human skeletal muscle. Journal of Physiology (London) 540, 387–395.Google Scholar
Schrauwen, P, Wagenmakers, AJ Marken Lichtenbelt, WD, Saris, WH & Westerterp, KR (2000) Increase in fat oxidation on a high-fat diet is accompanied by an increase in triglyceride-derived fatty acid oxidation. Diabetes 49, 640–646.Google Scholar
Starling, RD, Trappe, TA, Parcell, AC, Kerr, CG, Fink, WJ & Costill, DL (1997) Effects of diet on muscle triglyceride and endurance performance. Journal of Applied Physiology 82, 1185–1189.Google Scholar
Watt, MJ, Heigenhauser, GJF, Dyck, DJ & Spriet, LL, (2002a) Intramuscular triacylglycerol, glycogen and acetyl group metabolism during 4 h of moderate exercise in man. Journal of Physiology (London) 541, 969–978.Google Scholar
Watt, MJ, Heigenhauser, GJF, O'Neill, M & Spriet, LL (2003a) Hormone sensitive lipase activation and fatty acyl CoA content in human skeletal muscle during prolonged exercise. Journal of Applied Physiology 95, 314–321.Google Scholar
Watt, MJ, Heigenhauser, GJF & Spriet, LL (2002b) Intramuscular triacylglycerol utilization in human skeletal muscle during exercise: is there a controversy. Journal of Applied Physiology 93, 1185–1195.Google Scholar
Watt, MJ, Heigenhauser, GJF & Spriet, LL (2003b) Effects of dynamic exercise intensity on activation of hormone sensitive lipase in human skeletal muscle. Journal of Physiology (London) 547, 301–308.Google Scholar
Watt, MJ, Krustrup, P, Secher, NH, Saltin, B, Pedersen, BK & Febbraio, MA (2004) Glucose blunts hormone-sensitive lipase activity in contracting human skeletal muscle. American Journal of Physiology 286, E144–E150.Google Scholar
Watt, MJ, Steinberg, GR, Heigenhauser, GJF, Spriet, LL & Dyck, DJ, (2003c) Hormone sensitive lipase activity and triacylglycerol hydrolysis are decreased in rat soleus muscle by cyclopiazonic acid. American Journal of Physiology 285, E412–E419.Google Scholar
Watt, MJ, Stellingwerff, T, Heigenhauser, GJF & Spriet, LL (2003d) Adrenergic regulation of hormone sensitive lipase at rest and during moderate exercise in human skeletal muscle. Journal of Physiology (London) 550, 325–332.Google Scholar
Wojtaszewski, JF, Mourtzakis, M, Hillig, T, Saltin, B & Pilegaard, H (2002) Dissociation of AMPK activity and ACCβ phosphorylation in human muscle during prolonged exercise. Biochemical and Biophysical Research Communications 298, 309–316.Google Scholar
Xue, B, Greenberg, AG, Kraemer, FB & Zemel, MB (2001) Mechanisms of intracellular calcium ([Ca 2+ ]) inhibition of lipolysis in human adipocytes. FASEB Journal 15, 2527–2529.Google Scholar