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β‐adrenergic stimulation of skeletal muscle HSL can be overridden by AMPK signaling
Author(s) -
Watt Matthew J.,
Steinberg Gregory R.,
Chan Stanley,
Garnham Andrew,
Kemp Bruce E.,
Febbraio Mark A.
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-1067fje
Subject(s) - medicine , endocrinology , ampk , skeletal muscle , stimulation , glycogen , hormone sensitive lipase , chemistry , protein kinase a , contraction (grammar) , glycogenolysis , adipose tissue , phosphorylation , lipolysis , biochemistry
Hormone‐sensitive lipase (HSL), an important regulatory enzyme for triacylglycerol hydrolysis within skeletal muscle, is controlled by β‐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 β‐adrenergic stimulation of HSL activity. Eight male subjects completed 60 min of cycle exercise at 70% VO 2 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•kg –1 dm for CON and LG, respectively. AMPK α‐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•min –1 •kg –1 dm) in CON. The exercise‐induced increase in HSL activity was attenuated by AMPK α‐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.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 β‐adrenergic stimulation. However, the increased IMTG degradation in LG suggests factors other than HSL activity are important for IMTG degradation.