Effects of Plasma Adrenaline on Hormone‐Sensitive Lipase at Rest and during Moderate Exercise in Human Skeletal Muscle

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of intramuscular triacylglycerols (IMTGs), but HSL regulation is poorly understood in skeletal muscle. The present study measured human skeletal muscle HSL activity at rest and during 120 min of cycling at 60% of peak O2 uptake. Several putative HSL regulators were also measured, including muscle long-chain fatty acyl-CoA (LCFA CoA) and free AMP contents and plasma epinephrine and insulin concentrations. HSL activity increased from resting levels by 10 min of exercise (from 2.09 ± 0.19 to 2.56 ± 0.22 mmol · min-1 · kg dry mass-1, P < 0.05), increased further by 60 min (to 3.12 ± 0.27 mmol · min-1 · kg dry mass-1, P < 0.05), and decreased to near-resting rates after 120 min of cycling. Skeletal muscle LCFA CoA increased ( P < 0.05) above rest by 60 min (from 15.9 ± 3.0 to 50.4 ± 7.9 μmol/kg dry mass) and increased further by 120 min. Estimated free AMP increased ( P < 0.05) from rest to 60 min and was ∼20-fold greater than that at rest by 120 min. Epinephrine was increased above rest ( P < 0.05) at 60 (1.47 ± 0.15 nM) and 120 min (4.87 ± 0.76 nM) of exercise. Insulin concentrations decreased rapidly and were lower than resting levels by 10 min and continued to decrease throughout exercise. In summary, HSL activity was increased from resting levels by 10 min, increased further by 60 min, and decreased to near-resting values by 120 min. The increased HSL activity at 60 min was associated with the stimulating effect of increased epinephrine and decreased insulin levels. After 120 min, the decreased HSL activity was associated with the proposed inhibitory effects of increased free AMP. The accumulation of LCFA CoA in the 2nd h of exercise may also have reduced the flux through HSL and accounted for the reduction in IMTG utilization previously observed late in prolonged exercise.

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Regulation and role of hormone-sensitive lipase activity in human skeletal muscle

Proceedings of The Nutrition Society ◽

10.1079/pns2004360 ◽

2004 ◽

Vol 63 (2) ◽

pp. 315-322 ◽

Cited By ~ 25

Author(s):

Matthew J. Watt ◽

Lawrence L. Spriet

Keyword(s):

Skeletal Muscle ◽

Aerobic Exercise ◽

Human Skeletal Muscle ◽

Fatty Acyl ◽

Hormone Sensitive Lipase ◽

Moderate Intensity ◽

Control Points ◽

Moderate Intensity Exercise ◽

Hormone Sensitive

Hormone-sensitive lipase (HSL) is believed to play a regulatory role in initiating the degradation of intramuscular triacylglycerol (IMTG) in skeletal muscle. A series of studies designed to characterise the response of HSL to three stimuli: exercise of varying intensities and durations; adrenaline infusions; altered fuel supply have recently been conducted in human skeletal muscle. In an attempt to understand the regulation of HSL activity the changes in the putative intramuscular and hormonal regulators of the enzyme have also been measured. In human skeletal muscle at rest there is a high constitutive level of HSL activity, which is not a function of biopsy freezing. The combination of low adrenaline and Ca2+levels and resting levels of insulin appear to dictate the level of HSL activity at rest. During the initial minute of low and moderate aerobic exercise HSL is activated by contractions in the apparent absence of increases in circulating adrenaline. During intense aerobic exercise, adrenaline may contribute to the early activation of HSL. The contraction-induced activation may be related to increased Ca2+and/or other unknown intramuscular activators. As low- and moderate-intensity exercise continues beyond a few minutes, activation by adrenaline through the cAMP cascade may also occur. With prolonged moderate-intensity exercise beyond 1–2 h and sustained high-intensity exercise, HSL activity decreases despite continuing increases in adrenaline, possibly as a result of increasing accumulations of free AMP, activation of AMP kinase and phosphorylation of inhibitory sites on HSL. The existing work in human skeletal muscle also suggests that there are numerous levels of control involved in the regulation of IMTG degradation, with control points downstream from HSL also being important. For example, it must be remembered that the actual flux (IMTG degradation) through HSL may be allosterically inhibited during prolonged exercise as a result of the accumulation of long-chain fatty acyl-CoA.

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Hormone-sensitive lipase preferentially redistributes to lipid droplets associated with perilipin-5 in human skeletal muscle during moderate-intensity exercise

The Journal of Physiology ◽

10.1113/jp275502 ◽

2018 ◽

Vol 596 (11) ◽

pp. 2077-2090 ◽

Cited By ~ 7

Author(s):

Katie L. Whytock ◽

Sam O. Shepherd ◽

Anton J. M. Wagenmakers ◽

Juliette A. Strauss

Keyword(s):

Skeletal Muscle ◽

Lipid Droplets ◽

Human Skeletal Muscle ◽

Hormone Sensitive Lipase ◽

Moderate Intensity ◽

Moderate Intensity Exercise ◽

Hormone Sensitive ◽

Perilipin 5

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

Biochemical Journal ◽

10.1042/bj3400459 ◽

1999 ◽

Vol 340 (2) ◽

pp. 459-465 ◽

Cited By ~ 91

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.

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Molecular Mechanism of Corticosteroid-Induced Hyperglycemia

Pharmacy Reports ◽

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.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1999.277.5.e830 ◽

1999 ◽

Vol 277 (5) ◽

pp. E830-E837 ◽

Cited By ~ 7

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.

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