Beta-adrenergic stimulation of skeletal muscle HSL can be overridden by AMPK signaling.
Hormone-sensitive lipase (HSL), an important regulatory enzyme for triacylglycerol hydrolysis within skeletal muscle, is controlled by beta-adrenergic signaling as well as intrinsic factors related to contraction and energy turnover. In the current study, we tested the capacity of 5'AMP-activated protein kinase (AMPK) to suppress beta-adrenergic stimulation of HSL activity. Eight male subjects completed 60 min of cycle exercise at 70% VO2 peak on two occasions: either with normal (CON) or low (LG) pre-exercise muscle glycogen content, which is known to enhance exercise-induced AMPK activity. Muscle samples were obtained before and immediately after exercise. Pre-exercise glycogen averaged 375 +/- 35 and 163 +/- 27 mmol x kg(-1) dm for CON and LG, respectively. AMPK alpha-2 was not different between trials at rest and was increased (3.7-fold, P<0.05) by exercise during LG only. HSL activity did not differ between trials at rest and increased (0 min: 1.67 +/- 0.13; 60 min: 2.60 +/- 0.26 mmol x min(-1) x kg(-1) dm) in CON. The exercise-induced increase in HSL activity was attenuated by AMPK alpha-2 activation in LG. The attenuated HSL activity during LG occurred despite higher plasma epinephrine levels (60 min: CON, 1.96 +/- 0.29 vs LG, 4.25 +/- 0.60 nM, P<0.05) compared with CON. Despite the attenuated HSL activity in LG, IMTG was decreased by exercise (0 min: 27.1 +/- 2.0; 60 min: 22.5 +/- 2.0 mmol x kg(-1) dm, P<0.05), whereas no net reduction occurred in CON. To confirm the apparent effect of AMPK on HSL activity, we performed experiments in muscle cell culture. The epineprine-induced increase in HSL activity was totally attenuated (P<0.05) by AICAR administration in L6 myotubes. These data provide new evidence indicating that AMPK is a major regulator of skeletal muscle HSL activity that can override beta-adrenergic stimulation. However, the increased IMTG degradation in LG suggests factors other than HSL activity are important for IMTG degradation.
Watt
Matthew J
MJ
Skeletal Muscle Research Laboratory, School of Medical Sciences, Royal Melbourne Institute of Technology, Bundoora, Victoria, Australia. matthew.watt@rmit.edu.au
Steinberg
Gregory R
GR
Chan
Stanley
S
Garnham
Andrew
A
Kemp
Bruce E
BE
Febbraio
Mark A
MA
D055372:AMP-Activated Protein Kinases; D018663:Adrenergic Agents / Q000378:metabolism*; D004789:Enzyme Activation; D004837:Epinephrine / Q000097:blood / Q000378:metabolism; D015444:Exercise / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D008297:Male; D009097:Multienzyme Complexes / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction; D002787:Sterol Esterase / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D018663:Adrenergic Agents; D009097:Multienzyme Complexes; D014280:Triglycerides; D006003:Glycogen; C526181:PRKAA2 protein, human; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D002787:Sterol Esterase; D004837:Epinephrine