Hormone-sensitive lipase activity and fatty acyl-CoA content in human skeletal muscle during prolonged exercise

2003 ◽  
Vol 95 (1) ◽  
pp. 314-321 ◽  
Author(s):  
Matthew J. Watt ◽  
George J. F. Heigenhauser ◽  
Marcus O'Neill ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Prolonged Exercise ◽  
Dry Mass ◽  
Fatty Acyl ◽  
Hormone Sensitive Lipase ◽  
Inhibitory Effects ◽  
Hormone Sensitive ◽  
Hydrolysis Of ◽  
Long Chain

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.

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

2004 ◽  
Vol 63 (2) ◽  
pp. 315-322 ◽  
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.

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

Effects of reduced free fatty acid availability on hormone-sensitive lipase activity in human skeletal muscle during aerobic exercise

2004 ◽  
Vol 97 (5) ◽  
pp. 1938-1945 ◽  
Author(s):  
Marcus O'Neill ◽  
Matthew J. Watt ◽  
George J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Aerobic Exercise ◽  
Fat Oxidation ◽  
Dry Mass ◽  
Hormone Sensitive Lipase ◽  
Hormone Sensitive ◽  
Plasma Ffa ◽  
Muscle Biopsies

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of intramuscular triacylglycerol (IMTG); however, its regulation in skeletal muscle is poorly understood. To examine the effects of reduced free fatty acid (FFA) availability on HSL activity in skeletal muscle during aerobic exercise, 11 trained men exercised at 55% maximal O2 uptake for 40 min after the ingestion of nicotinic acid (NA) or nothing (control). Muscle biopsies were taken at rest and 5, 20, and 40 min of exercise. Plasma FFA were suppressed ( P < 0.05) in NA during exercise (∼0.40 ± 0.04 vs. ∼0.07 ± 0.01 mM). The respiratory exchange ratio (RER) was increased throughout exercise (0.020 + 0.008) after NA ingestion. However, the provision of energy from fat oxidation only decreased from 33% of the total in the control trial to 26% in the NA trial, suggesting increased IMTG oxidation in the NA trial. Mean HSL activity was 2.25 + 0.15 mmol·kg dry mass−1·min−1 at rest and increased ( P < 0.05) to 2.94 ± 0.20 mmol·kg dry mass−1·min−1 at 5 min in control. Contrary to the hypothesis, mean HSL was not activated to a greater extent in the NA trial during exercise (2.20 + 0.28 at rest to 2.88 + 0.21 mmol·kg dry mass−1·min−1 at 5 min). No further HSL increases were observed at 20 or 40 min in both trials. There was variability in the response to NA ingestion, as some subjects experienced a large increase in RER and decrease in fat oxidation, whereas other subjects experienced no shift in RER and maintained fat oxidation despite the reduced FFA availability in the NA trial. However, even in these subjects, HSL activity was not further increased during the NA trial. In conclusion, reduced plasma FFA availability accompanied by increased epinephrine concentration did not further activate HSL beyond exercise alone.

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

2003 ◽  
Vol 550 (1) ◽  
pp. 325-332 ◽  
Author(s):  
Matthew J. Watt ◽  
Trent Stellingwerff ◽  
George J. F. Heigenhauser ◽  
Lawrence L. Spriet
Keyword(s):  
Skeletal Muscle ◽  
Human Skeletal Muscle ◽  
Hormone Sensitive Lipase ◽  
Moderate Exercise ◽  
Plasma Adrenaline ◽  
Hormone Sensitive
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