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Sex differences in hormone-sensitive lipase expression, activity, and phosphorylation in skeletal muscle at rest and during exercise

¹The Copenhagen Muscle Research Centre, Department of Human Physiology, Institute of Exercise and Sport Sciences, University of Copenhagen, Copenhagen; ²The Copenhagen Muscle Research Centre, Department of Medical Physiology, Panum Institute, University of Copenhagen, Copenhagen; ³Division of Molecular Physiology, School of Life Sciences, University of Dundee, Dundee, United Kingdom; ⁴The Copenhagen Muscle Research Centre, Department of Molecular Muscle Biology, Rigshospitalet, Copenhagen; ⁵Department of Sport Science, University of Aarhus, Aarhus; ⁶Department of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen; and ⁷The Copenhagen Muscle Research Centre, Department of Rheumatology, Bispebjerg Hospital, Copenhagen, Denmark

Submitted 28 February 2006 ; accepted in final form 28 June 2006

Women have been shown to use more intramuscular triacylglycerol (IMTG) during exercise than men. To investigate whether this could be due to sex-specific regulation of hormone-sensitive lipase (HSL) and to use sex comparison as a model to gain further insight into HSL regulation, nine women and eight men performed bicycle exercise (90 min, 60% O_2peak), and skeletal muscle HSL expression, phosphorylation, and activity were determined. Supporting previous findings, basal IMTG content (P < 0.001) and net IMTG decrease during exercise (P < 0.01) were higher in women than in men and correlated significantly (r = 0.72, P = 0.001). Muscle HSL mRNA (80%, P = 0.11) and protein content (50%, P < 0.05) were higher in women than in men. HSL total activity increased during exercise (47%, P < 0.05) but did not differ between sexes. Accordingly, HSL specific activity (HSL activity per HSL protein content) increased during exercise (62%, P < 0.05) and was generally higher in men than in women (82%, P < 0.05). A similar pattern was observed for HSL Ser⁶⁵⁹ phosphorylation, suggesting a role in regulation of HSL activity. Likewise, plasma epinephrine increased during exercise (P < 0.05) and was higher in men than in women during the end of the exercise bout (P < 0.05). We conclude that, although HSL expression and Ser⁶⁵⁹ phosphorylation in skeletal muscle during exercise is sex specific, total muscle HSL activity measured in vitro was similar between sexes. The higher basal IMTG content in women compared with men is therefore the best candidate to explain the higher IMTG net hydrolysis during exercise in women.

intramuscular triacylglycerol; epinephrine; extracellular signal-regulated kinase

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