Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training.
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.
Alsted
Thomas J
TJ
University of Copenhagen, The August Krogh Bldg. 13, Universitetsparken, DK, 2100 Copenhagen, Denmark.
Nybo
Lars
L
Schweiger
Martina
M
Fledelius
Christian
C
Jacobsen
Poul
P
Zimmermann
Robert
R
Zechner
Rudolf
R
Kiens
Bente
B
D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D001706:Biopsy; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology*; D010766:Phosphorylation / Q000502:physiology; D010807:Physical Endurance / Q000502:physiology; D005082:Physical Exertion / Q000502:physiology*; D002787:Sterol Esterase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D014280:Triglycerides; D051048:Diacylglycerol O-Acyltransferase; D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; C439972:ABHD5 protein, human; D002787:Sterol Esterase; D008049:Lipase