Stimulation of hormone-sensitive lipase activity by contractions in rat skeletal muscle

2000 ◽  
Vol 351 (1) ◽  
pp. 207-214 ◽  
Author(s):  
Jozef LANGFORT ◽  
Thorkil PLOUG ◽  
Jacob IHLEMANN ◽  
Cecilia HOLM ◽  
Henrik GALBO
Keyword(s):  
Skeletal Muscle ◽  
Lipase Activity ◽  
Glycogen Phosphorylase ◽  
Time Course ◽  
Total Activity ◽  
Hormone Sensitive Lipase ◽  
Hormone Sensitive ◽  
Neutral Lipase ◽  
Glycogen Phosphorylase Activity ◽  
Muscle Triglyceride

Because the enzymic regulation of muscle triglyceride breakdown is poorly understood we studied whether neutral lipase in skeletal muscle is activated by contractions. Incubated soleus muscles from 70 g rats were electrically stimulated for 60min. Neutral lipase activity against triacylglycerol increased after 1 and 5min of contractions [0.36±0.02 (basal) versus 0.49±0.05 (1min) and 0.54±0.05 (5min) m-unit·mg of protein-1, means±S.E.M., P < 0.05]. After 10min the neutral lipase activity (0.40±0.05m-unit·mg of protein-1) had decreased to basal values (P > 0.05). The contraction-mediated increase in lipase activity was increased by ≈ 110% when muscle was stimulated in the presence of okadaic acid. Conversely, treatment of muscle homogenate with alkaline phosphatase completely reversed the contraction-mediated lipase activation. Lipase activity did not change during contractions when analysed in the presence of anti-hormone-sensitive-lipase (HSL) antibody [0.17±0.02 (basal) versus 0.21±0.02 (5min) m-unit·mg of protein-1, P > 0.05]. Furthermore, immunoprecipitation with affinity-purified anti-HSL antibody reduced muscle-HSL protein concentration by 81±4% and caused similar reductions in lipase activity against triacylglycerol and in the contraction-induced increase in this activity. Neither prior sympathectomy [0.33±0.02 (basal) versus 0.53±0.06 (5min) m-unit·mg of protein-1, P < 0.05] nor propranolol impaired the lipase response to contractions. Glycogen phosphorylase activity in the absence of AMP increased after 1min [27.3±3.1 versus 8.9±1.8% (activity without AMP/total activity with AMP), P < 0.05] and returned to basal levels after 5min. In conclusion, skeletal-muscle-immunoreactive HSL is transiently stimulated by contractions and the mechanism probably involves phosphorylation. The time course of HSL activation is similar to that of glycogen phosphorylase. Apparently, the two enzymes are regulated in parallel by contraction-induced as well as hormonal mechanisms, allowing simultaneous recruitment of all major extra- and intra-muscular energy stores.

scholarly journals Expression of hormone-sensitive lipase and its regulation by adrenaline in skeletal muscle

1999 ◽  
Vol 340 (2) ◽  
pp. 459-465 ◽  
Author(s):  
Jozef LANGFORT ◽  
Thorkil PLOUG ◽  
Jacob IHLEMANN ◽  
Michele SALDO ◽  
Cecilia HOLM ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Soleus Muscle ◽  
Lipase Activity ◽  
Glycogen Phosphorylase ◽  
Hormone Sensitive Lipase ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Hormone Sensitive ◽  
Neutral Lipase

The enzymic regulation of triacylglycerol breakdown in skeletal muscle is poorly understood. Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying demonstrated the presence of immunoreactive hormone-sensitive lipase (HSL), with the concentrations in soleus and diaphragm being more than four times the concentrations in extensor digitorum longus and epitrochlearis muscles. Neutral lipase activity determined under conditions optimal for HSL varied directly with immunoreactivity. Expressed relative to triacylglycerol content, neutral lipase activity in soleus muscle was about 10 times that in epididymal adipose tissue. In incubated soleus muscle, both neutral lipase activity against triacylglycerol (but not against a diacylglycerol analogue) and glycogen phosphorylase activity increased in response to adrenaline (epinephrine). The lipase activation was completely inhibited by anti-HSL antibody and by propranolol. The effect of adrenaline could be mimicked by incubation of crude supernatant from control muscle with the catalytic subunit of cAMP-dependent protein kinase, while no effect of the kinase subunit was seen with supernatant from adrenaline-treated muscle. The results indicate that HSL is present in skeletal muscle and is stimulated by adrenaline via β-adrenergic activation of cAMP-dependent protein kinase. The concentration of HSL is higher in oxidative than in glycolytic muscle, and the enzyme is activated in parallel with glycogen phosphorylase.

scholarly journals Regulation and role of hormone-sensitive lipase in rat skeletal muscle

2004 ◽  
Vol 63 (2) ◽  
pp. 309-314 ◽  
Author(s):  
Morten Donsmark ◽  
Jozef Langfort ◽  
Cecilia Holm ◽  
Thorkil Ploug ◽  
Henrik Galbo
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Energy Content ◽  
Hormone Sensitive Lipase ◽  
Fibre Types ◽  
Muscle Fibre Types ◽  
Muscle Fibres ◽  
Energy Store ◽  
Hormone Sensitive ◽  
Neutral Lipase

Intramyocellular triacylglycerol (TG) is an important energy store, and the energy content of this depot is higher than the energy content of the muscle glycogen depot. It has recently been shown that the mobilization of fatty acids from this TG pool may be regulated by the neutral lipase hormone-sensitive lipase (HSL). This enzyme is known to be rate limiting for intracellular TG hydrolysis in adipose tissue. The presence of HSL has been demonstrated in all muscle fibre types by Western blotting of muscle fibres isolated by collagenase treatment or after freeze-drying. The content of HSL varies between fibre types, being higher in oxidative fibres than in glycolytic fibres. When analysed under conditions optimal for“ HSL, neutral lipase activity in muscle can be stimulated by adrenaline as well as by contractions. These increases are abolished by the presence of anti-HSL antibody during analysis. Moreover, immunoprecipitation with affinity-purified anti-HSL antibody causes similar reductions in muscle HSL protein concentration and in measured neutral lipase responses to contractions. The immunoreactive HSL in muscle is stimulated by adrenaline via β-adrenergic activation of cAMP-dependent protein kinase (PKA). From findings in adipocytes it is likely that PKA phosphorylates HSL at residues Ser563, Ser659and Ser660. Contraction probably also enhances muscle HSL activity by phosphorylation, because the contraction-induced increase in HSL activity is elevated by the protein phosphatase inhibitor okadaic acid and reversed by alkaline phosphatase. A novel signalling pathway in muscle by which HSL activity may be stimulated by protein kinase C (PKC) via extracellular signal-regulated kinase (ERK) has been demonstrated. In contrast to previous findings in adipocytes, in muscle the activation of ERK is not necessary for stimulation of HSL by adrenaline. However, contraction-induced HSL activation is mediated by PKC, at least partly via the ERK pathway. In fat cells ERK is known to phosphorylate HSL at Ser600. Hence, phosphorylation of different sites may explain the finding that in muscle the effects of contractions and adrenaline on HSL activity are partially additive. In line with the view that the two stimuli act by different mechanisms, training increases contraction-mediated HSL activation but diminishes adrenaline-mediated HSL activation in muscle. In conclusion, HSL is present in skeletal muscle and can be activated by phosphorylation in response to both adrenaline and muscle contractions. Training increases contraction-mediated HSL activation, but decreases adrenaline-mediated HSL activation in muscle.

scholarly journals Regulation of hormone-sensitive lipase activity and Ser563and Ser565phosphorylation in human skeletal muscle during exercise

2004 ◽  
Vol 560 (2) ◽  
pp. 551-562 ◽  
Author(s):  
Carsten Roepstorff ◽  
Bodil Vistisen ◽  
Morten Donsmark ◽  
Jakob N. Nielsen ◽  
Henrik Galbo ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipase Activity ◽  
Human Skeletal Muscle ◽  
Hormone Sensitive Lipase ◽  
Hormone Sensitive

Sex differences in hormone-sensitive lipase expression, activity, and phosphorylation in skeletal muscle at rest and during exercise

2006 ◽  
Vol 291 (5) ◽  
pp. E1106-E1114 ◽  
Author(s):  
Carsten Roepstorff ◽  
Morten Donsmark ◽  
Maja Thiele ◽  
Bodil Vistisen ◽  
Greg Stewart ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Specific Activity ◽  
Exercise Bout ◽  
Total Activity ◽  
Hormone Sensitive Lipase ◽  
Expression Activity ◽  
Hormone Sensitive ◽  
Specific Regulation

Women have been shown to use more intramuscular triacylglycerol (IMTG) during exercise than men. To investigate whether this could be due to sex-specific regulation of hormone-sensitive lipase (HSL) and to use sex comparison as a model to gain further insight into HSL regulation, nine women and eight men performed bicycle exercise (90 min, 60% V̇o2peak), and skeletal muscle HSL expression, phosphorylation, and activity were determined. Supporting previous findings, basal IMTG content ( P < 0.001) and net IMTG decrease during exercise ( P < 0.01) were higher in women than in men and correlated significantly ( r = 0.72, P = 0.001). Muscle HSL mRNA (80%, P = 0.11) and protein content (50%, P < 0.05) were higher in women than in men. HSL total activity increased during exercise (47%, P < 0.05) but did not differ between sexes. Accordingly, HSL specific activity (HSL activity per HSL protein content) increased during exercise (62%, P < 0.05) and was generally higher in men than in women (82%, P < 0.05). A similar pattern was observed for HSL Ser659 phosphorylation, suggesting a role in regulation of HSL activity. Likewise, plasma epinephrine increased during exercise ( P < 0.05) and was higher in men than in women during the end of the exercise bout ( P < 0.05). We conclude that, although HSL expression and Ser659 phosphorylation in skeletal muscle during exercise is sex specific, total muscle HSL activity measured in vitro was similar between sexes. The higher basal IMTG content in women compared with men is therefore the best candidate to explain the higher IMTG net hydrolysis during exercise in women.

Glucose ingestion blunts hormone-sensitive lipase activity in contracting human skeletal muscle

2004 ◽  
Vol 286 (1) ◽  
pp. E144-E150 ◽  
Author(s):  
Matthew J. Watt ◽  
Peter Krustrup ◽  
Niels H. Secher ◽  
Bengt Saltin ◽  
Bente K. Pedersen ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Lipase Activity ◽  
Femoral Vein ◽  
Dry Mass ◽  
Hormone Sensitive Lipase ◽  
Arterial Blood ◽  
Carbohydrate Feeding ◽  
Glucose Ingestion ◽  
Hormone Sensitive ◽  
Exercise Muscle

To examine the effect of attenuated epinephrine and elevated insulin on intramuscular hormone sensitivity lipase activity (HSLa) during exercise, seven men performed 120 min of semirecumbent cycling (60% peak pulmonary oxygen uptake) on two occasions while ingesting either 250 ml of a 6.4% carbohydrate (GLU) or sweet placebo (CON) beverage at the onset of, and at 15 min intervals throughout, exercise. Muscle biopsies obtained before and immediately after exercise were analyzed for HSLa. Blood samples were simultaneously obtained from a brachial artery and a femoral vein before and during exercise, and leg blood flow was measured by thermodilution in the femoral vein. Net leg glycerol and lactate release and net leg glucose and free fatty acid (FFA) uptake were calculated from these measures. Insulin and epinephrine were also measured in arterial blood before and throughout exercise. During GLU, insulin was elevated (120 min: CON, 11.4 ± 2.4, GLU, 35.3 ± 6.9 pM, P < 0.05) and epinephrine suppressed (120 min: CON, 6.1 ± 2.5, GLU, 2.1 ± 0.9 nM; P < 0.05) compared with CON. Carbohydrate feeding also resulted in suppressed ( P < 0.05) HSLa relative to CON (120 min: CON, 1.71 ± 0.18, GLU, 1.27 ± 0.16 mmol·min-1·kg dry mass-1). There were no differences in leg lactate or glycerol release when trials were compared, but leg FFA uptake was lower (120 min: CON, 0.29 ± 0.06, GLU, 0.82 ± 0.09 mmol/min) and leg glucose uptake higher (120 min: CON, 3.16 ± 0.59, GLU, 1.37 ± 0.37 mmol/min) in GLU compared with CON. These results demonstrate that circulating insulin and epinephrine play a role in HSLa in contracting skeletal muscle.

scholarly journals Stimulation of hormone-sensitive lipase activity by contractions in rat skeletal muscle

2000 ◽  
Vol 351 (1) ◽  
pp. 207 ◽  
Author(s):  
Jozef LANGFORT ◽  
Thorkil PLOUG ◽  
Jacob IHLEMANN ◽  
Cecilia HOLM ◽  
Henrik GALBO
Keyword(s):  
Skeletal Muscle ◽  
Lipase Activity ◽  
Hormone Sensitive Lipase ◽  
Rat Skeletal Muscle ◽  
Hormone Sensitive ◽  
Stimulation Of
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