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Journal of Lipid Research, Vol. 47, 2392-2399, November 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine

Clara Prats^1,*, Morten Donsmark^*, Klaus Qvortrup, Constantine Londos, Carole Sztalryd^**, Cecilia Holm, Henrik Galbo and Thorkil Ploug^*

^* Copenhagen Muscle Research Center, Department of Medical Physiology, Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark
Department of Medical Anatomy, Panum Institute, University of Copenhagen, DK-2200 Copenhagen N, Denmark
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-8028
^** Geriatric Research, Education, and Clinical Center, Baltimore Veterans Affairs Health Care Center, Department of Medicine, School of Medicine, University of Maryland, Baltimore, MD 21201
Department of Experimental Medical Science, University of Lund, BMC C11, SE-221 84, Lund, Sweden
Copenhagen Muscle Research Center, Department of Rheumatology, Bispebjerg Hospital, DK-2400 Copenhagen NV, Denmark

Published, JLR Papers in Press, August 12, 2006.

¹ To whom correspondence should be addressed. e-mail: cprats{at}mfi.ku.dk

A better understanding of skeletal muscle lipid metabolism is needed to identify the molecular mechanisms relating intramuscular triglyceride (IMTG) to muscle metabolism and insulin sensitivity. An increasing number of proteins have been reported to be associated with intracellular triglyceride (TG), among them the PAT family members: perilipin, ADRP (for adipocyte differentiation-related protein), and TIP47 (for tail-interacting protein of 47 kDa). Hormone-sensitive lipase (HSL) is thought to be the major enzyme responsible for IMTG hydrolysis in skeletal muscle. In adipocytes, regulation of HSL by intracellular redistribution has been demonstrated. The existence of such regulatory mechanisms in skeletal muscle has long been hypothesized but has never been demonstrated. The aim of this study was to characterize the PAT family proteins associated with IMTG and to investigate the effect of epinephrine stimulation or muscle contraction on skeletal muscle TG content and HSL intracellular distribution. Rat soleus muscles were either incubated with epinephrine or electrically stimulated for 15 min. Single muscle fibers were used for morphological analysis by confocal and transmission electron microscopy. We show a decrease in IMTG in response to both lipolytic stimuli. Furthermore, we identify two PAT family proteins, ADRP and TIP47, associated with IMTG. Finally, we demonstrate HSL translocation to IMTG and ADRP after stimulation with epinephrine or contraction.

Supplementary key words lipid metabolism regulation • skeletal muscle • hormone-sensitive lipase • adipocyte differentiation-related protein • tail-interacting protein of 47 kDa

Abbreviations: ADRP, adipocyte differentiation-related protein; HSL, hormone-sensitive lipase; IMTG, intramuscular triglyceride; LD, lipid droplet; PKA, cyclic AMP-dependent protein kinase; TEM, transmission electron microscopy; TG, triglyceride; TIP47, tail-interacting protein of 47 kDa

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