scholarly journals Hormone-Sensitive Lipase Serine Phosphorylation and Glycerol Exchange Across Skeletal Muscle in Lean and Obese Subjects: Effect of  -Adrenergic Stimulation

Diabetes ◽  
2008 ◽  
Vol 57 (7) ◽  
pp. 1834-1841 ◽  
Author(s):  
J. W.E. Jocken ◽  
C. Roepstorff ◽  
G. H. Goossens ◽  
P. van der Baan ◽  
M. van Baak ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Serine Phosphorylation ◽  
Hormone Sensitive Lipase ◽  
Adrenergic Stimulation ◽  
Hormone Sensitive ◽  
Obese Subjects

Adrenergic regulation of HSL serine phosphorylation and activity in human skeletal muscle during the onset of exercise

2006 ◽  
Vol 291 (4) ◽  
pp. R1094-R1099 ◽  
Author(s):  
Jason L. Talanian ◽  
Rebecca J. Tunstall ◽  
Matthew J. Watt ◽  
Mylinh Duong ◽  
Christopher G. R. Perry ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Cyclic Amp ◽  
High Intensity ◽  
Human Skeletal Muscle ◽  
High Intensity Exercise ◽  
Serine Phosphorylation ◽  
Hormone Sensitive Lipase ◽  
Peak Oxygen Consumption ◽  
Adrenergic Stimulation ◽  
Arterial Blood

Skeletal muscle hormone-sensitive lipase (HSL) activity is increased by contractions and increases in blood epinephrine (EPI) concentrations and cyclic AMP activation of the adrenergic pathway during prolonged exercise. To determine the importance of hormonal stimulation of HSL activity during the onset of moderate- and high-intensity exercise, nine men [age 24.3 ± 1.2 yr, 80.8 ± 5.0 kg, peak oxygen consumption (V̇o2 peak) 43.9 ± 3.6 ml·kg−1·min−1] cycled for 1 min at ∼65% V̇o2 peak, rested for 60 min, and cycled at ∼90% V̇o2 peak for 1 min. Skeletal muscle biopsies were taken pre- and postexercise, and arterial blood was sampled throughout exercise. Arterial EPI increased ( P < 0.05) postexercise at 65% (0.45 ± 0.10 to 0.78 ± 0.27 nM) and 90% V̇o2 peak (0.57 ± 0.34 to 1.09 ± 0.50 nM). HSL activity increased ( P < 0.05) following 1 min of exercise at 65% V̇o2 peak [1.05 ± 0.39 to 1.78 ± 0.54 mmol·min−1·kg dry muscle (dm)−1] and 90% V̇o2 peak (1.07 ± 0.24 to 1.91 ± 0.62 mmol·min−1·kg dm−1). Cyclic AMP content also increased ( P < 0.05) at both exercise intensities (65%: 1.52 ± 0.67 to 2.75 ± 1.12, 90%: 1.85 ± 0.65 to 2.64 ± 0.93 μmol/kg dm). HSL Ser660 phosphorylation (∼55% increase) and ERK1/2 phosphorylation (∼33% increase) were augmented following exercise at both intensities, whereas HSL Ser563 and Ser565 phosphorylation were not different from rest. The results indicate that increases in arterial EPI concentration during the onset of moderate- and high-intensity exercise increase cyclic AMP content, which results in the phosphorylation of HSL Ser660. This adrenergic stimulation contributes to the increase in HSL activity that occurs in human skeletal muscle in the first minute of exercise at 65% and 90% V̇o2 peak.

Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue

2006 ◽  
Vol 290 (3) ◽  
pp. E500-E508 ◽  
Author(s):  
Matthew J. Watt ◽  
Anna G. Holmes ◽  
Srijan K. Pinnamaneni ◽  
Andrew P. Garnham ◽  
Gregory R. Steinberg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Venous Blood ◽  
Serine Phosphorylation ◽  
Hormone Sensitive Lipase ◽  
Ampk Activation ◽  
Adrenergic Stimulation ◽  
L6 Myotubes ◽  
Specific Regulation

Hormone-sensitive lipase (HSL) is important for the degradation of triacylglycerol in adipose and muscle tissue, but the tissue-specific regulation of this enzyme is not fully understood. We investigated the effects of adrenergic stimulation and AMPK activation in vitro and in circumstances where AMPK activity and catecholamines are physiologically elevated in humans in vivo (during physical exercise) on HSL activity and phosphorylation at Ser563 and Ser660, the PKA regulatory sites, and Ser565, the AMPK regulatory site. In human experiments, skeletal muscle, subcutaneous adipose and venous blood samples were obtained before, at 15 and 90 min during, and 120 min after exercise. Skeletal muscle HSL activity was increased by ∼80% at 15 min compared with rest and returned to resting rates at the cessation of and 120 min after exercise. Consistent with changes in plasma epinephrine, skeletal muscle HSL Ser563 and Ser660 phosphorylation were increased by 27% at 15 min ( P < 0.05), remained elevated at 90 min, and returned to preexercise values postexercise. Skeletal muscle HSL Ser565 phosphorylation and AMPK signaling were increased at 90 min during, and after, exercise. Phosphorylation of adipose tissue HSL paralleled changes in skeletal muscle in vivo, except HSL Ser660 was elevated 80% in adipose compared with 35% in skeletal muscle during exercise. Studies in L6 myotubes and 3T3-L1 adipocytes revealed important tissue differences in the regulation of HSL. AMPK inhibited epinephrine-induced HSL activity in L6 myotubes and was associated with reduced HSL Ser660 but not Ser563 phosphorylation. HSL activity was reduced in L6 myotubes expressing constitutively active AMPK, confirming the inhibitory effects of AMPK on HSL activity. Conversely, in 3T3-L1 adipocytes, AMPK activation after epinephrine stimulation did not prevent HSL activity or glycerol release, which coincided with maintenance of HSL Ser660 phosphorylation. Taken together, these data indicate that HSL activity is maintained in the face of AMPK activation as a result of elevated HSL Ser660 phosphorylation in adipose tissue but not skeletal muscle.

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 Molecular Mechanism of Corticosteroid-Induced Hyperglycemia

10.51511/pr.1 ◽  
2021 ◽  
Author(s):  
Destika Ambar Sari ◽  
Galih Samodra ◽  
Ikhwan Yuda Kusuma
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Immunosuppressive Drugs ◽  
Hormone Sensitive Lipase ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Hormone Sensitive ◽  
Beta Cell Response

Corticosteroids are widely used as strong anti-inflammatory and immunosuppressive drugs to treat various diseases. However, the use of corticosteroids can cause several side effects, such as hyperglycemia. This review aims to examine the effect of corticosteroids on increasing glucose in molecular levels based on literature studies. A literature searching was carried out on the PubMed, Science Direct, and Google Scholar databases published in 2010-2020. Corticosteroids can cause an increase in blood glucose levels by several mechanisms. In the liver, glucocorticoids increase endogenous plasma glucose and stimulate gluconeogenesis. Glucocorticoids increase the production of non-esterified fatty acids which affect the signal transduction of insulin receptor substrate-1 in skeletal muscle. In adipose, glucocorticoids increase lipolysis and visceral adiposity through increased transcription and expression of protein adipose triglyceride lipase and hormone-sensitive lipase. In pancreatic beta cells, glucocorticoids directly inhibit the beta cell response to glucose through the role of protein kinase B and protein kinase C. At the molecular level, corticosteroids can cause hyperglycemia through mechanisms in the liver, skeletal muscle tissue, adipose tissue, and pancreatic beta cells.

Lack of skeletal muscle uncoupling protein 2 and 3 mRNA induction during fasting in type-2 diabetic subjects

1999 ◽  
Vol 277 (5) ◽  
pp. E830-E837 ◽  
Author(s):  
Hubert Vidal ◽  
Dominique Langin ◽  
Fabrizio Andreelli ◽  
Laurence Millet ◽  
Dominique Larrouy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Calorie Restriction ◽  
Uncoupling Protein ◽  
Hormone Sensitive Lipase ◽  
Nonesterified Fatty Acid ◽  
Diabetic Patients ◽  
Mrna Levels ◽  
Hormone Sensitive ◽  
Type 2 Diabetic

Skeletal muscle uncoupling protein 2 and 3 (UCP-2 and UCP-3) mRNA levels are increased during calorie restriction in lean and nondiabetic obese subjects. In this work, we have investigated the effect of a 5-day hypocaloric diet (1,045 kJ/day) on UCP-2 and UCP-3 gene expression in the skeletal muscle of type-2 diabetic obese patients. Before the diet, UCP-2 and UCP-3 mRNA levels were more abundant in diabetic than in nondiabetic subjects. The long (UCP-3L) and short (UCP-3S) forms of UCP-3 transcripts were expressed at similar levels in nondiabetic subjects, but UCP-3S transcripts were twofold more abundant than UCP-3Ltranscripts in the muscle of diabetic patients. Calorie restriction induced a two- to threefold increase in UCP-2 and UCP-3 mRNA levels in nondiabetic patients. No change was observed in type-2 diabetic patients. Variations in plasma nonesterified fatty acid level were positively correlated with changes in skeletal muscle UCP-3L( r = 0.6, P < 0.05) and adipose tissue hormone-sensitive lipase ( r = 0.9, P < 0.001) mRNA levels. Lack of increase in plasma nonesterified fatty acid level and in hormone-sensitive lipase upregulation in diabetic patients during the diet strengthens the hypothesis that fatty acids are associated with the upregulation of uncoupling proteins during calorie restriction.

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.

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