Phosphorylation of adipose triglyceride lipase Ser(404) is not related to 5'-AMPK activation during moderate-intensity exercise in humans.
Intramyocellular triacylglycerol provides fatty acid substrate for ATP generation in contracting muscle. The protein adipose triglyceride lipase (ATGL) is a key regulator of triacylglycerol lipolysis and whole body energy metabolism at rest and during exercise, and ATGL activity is reported to be enhanced by 5'-AMP-activated protein kinase (AMPK)-mediated phosphorylation at Ser(406) in mice. This is a curious observation, because AMPK activation reduces lipolysis in several cell types. We investigated whether the phosphorylation of ATGL Ser(404) (corresponding to murine Ser(406)) was increased during exercise in human skeletal muscle and with pharmacological AMPK activation in myotubes in vitro. In human experiments, skeletal muscle and venous blood samples were obtained from recreationally active male subjects before and at 5 and 60 min during exercise. ATGL Ser(404) phosphorylation was not increased from rest during exercise, but ATGL Ser(404) phosphorylation correlated with myosin heavy chain 1 expression, suggesting a possible fiber type dependency. ATGL Ser(404) phosphorylation was not related to increases in AMPK activity, and immunoprecipitation experiments indicated no interaction between AMPK and ATGL. Rather, ATGL Ser(404) phosphorylation was associated with protein kinase A (PKA) signaling. ATGL Ser(406) phosphorylation in C(2)C(12) myotubes was unaffected by 5-aminoimidazole-4-carboxaminde-1-β-d-ribofuranoside, an AMPK activator, and the PKA activator forskolin. Our results demonstrate that ATGL Ser(404) phosphorylation is not increased in mixed skeletal muscle during moderate-intensity exercise and that AMPK does not appear to be an activating kinase for ATGL Ser(404/406) in skeletal muscle.
Biology of Lipid Metabolism Laboratory, Department of Physiology, Monash University, Clayton, Victoria, Australia.
Rachael R
RR
Mason
Ruth C R
RC
Meex
Robert
R
Lee-Young
Benedict J
BJ
Canny
Matthew J
MJ
Watt
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000328:Adult; D000620:Aminoimidazole Carboxamide / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D008049:Lipase / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism*; D055815:Young Adult; D000217:Acyltransferases
D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide; D001786:Blood Glucose; D005576:Colforsin; D005230:Fatty Acids, Nonesterified; D019344:Lactic Acid; D008049:Lipase; D012694:Serine; C526181:PRKAA2 protein, human; C526180:PRKAA1 protein, human; C494794:PNPLA2 protein, human; D000217:Acyltransferases