Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training

1 Copenhagen Muscle Research Centre, Section of Human Physiology, Department of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark; 2 Institute of Molecular Biosciences, University of Graz, Graz, Austria; and 3 Diabetes Research Unit, Novo Nordisk A/S, Måløv, Denmark Submitted 13 November 2008 ; accepted in final form 18 December 2008 Mobilization of fatty acids from stored triacylglycerol (TG) in adipose tissue and skeletal muscle [intramyocellular triacylglycerol (IMTG)] requires activity of lipases. Although exercise training increases the lipolytic capacity of skeletal muscle, the expression of hormone-sensitive lipase (HSL) is not changed. Recently, adipose triglyceride lipase (ATGL) was identified as a TG-specific lipase in various rodent tissues. To investigate whether human skeletal muscle ATGL protein is regulated by endurance exercise training, 10 healthy young men completed 8 wk of supervised endurance exercise training. Western blotting analysis on lysates of skeletal muscle biopsy samples revealed that exercise training induced a twofold increase in skeletal muscle ATGL protein content. In contrast to ATGL, expression of comparative gene identification 58 (CGI-58), the activating protein of ATGL, and HSL protein was not significantly changed after the training period. The IMTG concentration was significantly decreased by 28% at termination of the training program compared with before. HSL-phoshorylation at Ser 660 was increased, HSL-Ser 659 phosporylation was unchanged, and HSL-phoshorylation at Ser 565 was decreased altogether, indicating an enhanced basal activity of this lipase. No change was found in the expression of diacylglycerol acyl transferase 1 (DGAT1) after training. Inhibition of HSL with a monospecific, small molecule inhibitor (76-0079) and stimulation of ATGL with CGI-58 revealed that significant ATGL activity is present in human skeletal muscle. These results suggest that ATGL in addition to HSL may be important for human skeletal muscle lipolysis. comparative gene identification 58; hormone sensitive lipase; diacylglycerol acyl transferase 1; intramyocellular triacylglycerol; lipolysis Address for reprint requests and other correspondence: B. Kiens, Univ. of Copenhagen, The August Krogh Bldg. 13, Universitetsparken, DK, 2100 Copenhagen, Denmark (e-mail: bkiens{at}ifi.ku.dk )