Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue

Watt, Matthew J., Holmes, Anna G., Pinnamaneni, Srijan K., Garnham, Andrew, Steinberg, Gregory R., Kemp, Bruce E. and Febbraio, Mark A. 2006, Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue, American journal of physiology. Endocrinology and metabolism, vol. 290, no. 3, pp. 500-508, doi: 10.1152/ajpendo.00361.2005.

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Title Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue
Author(s) Watt, Matthew J.
Holmes, Anna G.
Pinnamaneni, Srijan K.
Garnham, Andrew
Steinberg, Gregory R.
Kemp, Bruce E.
Febbraio, Mark A.
Journal name American journal of physiology. Endocrinology and metabolism
Volume number 290
Issue number 3
Start page 500
End page 508
Publisher American Physiological Society
Place of publication Bethesda, Md.
Publication date 2006-03
ISSN 0193-1849
Keyword(s) hormone-sensitive lipase
fat metabolism
AMP-activated protein kinase
Summary Hormone-sensitive lipase (HSL) is important for the degradation of triacylglycerol in adipose and muscle tissue, but the tissue-specific regulation of this enzyme is not fully understood. We investigated the effects of adrenergic stimulation and AMPK activation in vitro and in circumstances where AMPK activity and catecholamines are physiologically elevated in humans in vivo (during physical exercise) on HSL activity and phosphorylation at Ser563 and Ser660, the PKA regulatory sites, and Ser565, the AMPK regulatory site. In human experiments, skeletal muscle, subcutaneous adipose and venous blood samples were obtained before, at 15 and 90 min during, and 120 min after exercise. Skeletal muscle HSL activity was increased by ~80% at 15 min compared with rest and returned to resting rates at the cessation of and 120 min after exercise. Consistent with changes in plasma epinephrine, skeletal muscle HSL Ser563 and Ser660 phosphorylation were increased by 27% at 15 min (P < 0.05), remained elevated at 90 min, and returned to preexercise values postexercise. Skeletal muscle HSL Ser565 phosphorylation and AMPK signaling were increased at 90 min during, and after, exercise. Phosphorylation of adipose tissue HSL paralleled changes in skeletal muscle in vivo, except HSL Ser660 was elevated 80% in adipose compared with 35% in skeletal muscle during exercise. Studies in L6 myotubes and 3T3-L1 adipocytes revealed important tissue differences in the regulation of HSL. AMPK inhibited epinephrine-induced HSL activity in L6 myotubes and was associated with reduced HSL Ser660 but not Ser563 phosphorylation. HSL activity was reduced in L6 myotubes expressing constitutively active AMPK, confirming the inhibitory effects of AMPK on HSL activity. Conversely, in 3T3-L1 adipocytes, AMPK activation after epinephrine stimulation did not prevent HSL activity or glycerol release, which coincided with maintenance of HSL Ser660 phosphorylation. Taken together, these data indicate that HSL activity is maintained in the face of AMPK activation as a result of elevated HSL Ser660 phosphorylation in adipose tissue but not skeletal muscle.
Language eng
DOI 10.1152/ajpendo.00361.2005
Field of Research 111601 Cell Physiology
HERDC Research category C1 Refereed article in a scholarly journal
HERDC collection year 2005
Copyright notice ©2006, American Physiological Society
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Document type: Journal Article
Collections: Faculty of Health
School of Exercise and Nutrition Sciences
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