Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.1.79 (hormone-sensitive lipase)
2,163 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipocyte glucose transport can be impaired by prolonged hyperglycemic conditions. However, at the whole body level, lipolysis is quantitatively a more important function of adipocytes than glucose uptake. We have therefore investigated the effect of prolonged high glucose and insulin on adipocyte lipolysis in basal conditions or with maximal concentrations of adenosine deaminase (ADA), dibutyryl cyclic-AMP (dbcAMP), or isoproterenol (ISO). Neither insulin nor glucose alone affected basal or maximally stimulated lipolysis. However, insulin plus glucose increased the rate of ADA-, dbcAMP-, and ISO-stimulated lipolysis by 40-65%, and the effect was maximal by 8 h. When insulin was kept constant, the half-maximally effective concentration (EC50) of glucose was approximately 2.5 mmol/l. We also demonstrated that the effect is not glutamine-dependent and does not induce insulin resistance of lipolysis. Because the effect of insulin and glucose was evident whether lipolysis was stimulated by ADA, dbcAMP, or ISO, we hypothesized that the expression of the rate-limiting enzyme for lipolysis, hormone-sensitive lipase (HSL), was increased. Our results show that insulin plus glucose-treated cells contain approximately 40% more HSL protein than control cells, in good agreement with the increase in maximally stimulated lipolysis. We conclude that hyperglycemic-hyperinsulinemic conditions increase basal and maximal adipocyte lipolysis by a mechanism that is not glutamine-dependent and involves maintenance of cellular concentrations of HSL. The results also provide evidence that factors other than translocation of HSL to the lipid droplet are necessary to activate the enzyme.
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PMID:Long-term regulation of lipolysis and hormone-sensitive lipase by insulin and glucose. 1048 May 96

Decreased lipolytic effect of catecholamines in adipose tissue has repeatedly been demonstrated in obesity and may be a cause of excess accumulation of body fat. However, the mechanisms behind this lipolysis defect are unclear. The role of hormone-sensitive lipase was examined using abdominal subcutaneous adipocytes from 34 obese drug-free and otherwise healthy males or females and 14 non-obese control subjects. The enzyme catalyzes the rate-limiting step of the lipolysis pathway. The maximum lipolytic capacity of fat cells was significantly decreased in obesity when measured using either a non-selective beta-adrenergic receptor agonist (isoprenaline) or a phosphodiesterase resistant cyclic AMP analogue (dibutyryl cyclic AMP). Likewise, enzyme activity, protein expression, and mRNA of hormone-sensitive lipase were significantly decreased in adipocytes of obese subjects. The findings were not influenced by age or gender. The data suggest that a decreased expression of hormone-sensitive lipase in subcutaneous fat cells, which in turn causes decreased enzyme function and impaired lipolytic capacity of adipocytes, is present in obesity. Impaired expression of the hormone-sensitive lipase gene might at least in part explain the enzyme defect.
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PMID:Decreased expression and function of adipocyte hormone-sensitive lipase in subcutaneous fat cells of obese subjects. 1055 9

Luminescence in Vibrio fischeri is controlled by a population density-responsive regulatory mechanism called quorum sensing. Elements of the mechanism include: LuxI, an acyl-homoserine lactone (acyl-HSL) synthase that directs synthesis of the diffusible signal molecule, 3-oxo-hexanoyl-HSL (V. fischeri autoinducer-1, VAI-1); LuxR, a transcriptional activator protein necessary for response to VAI-1; GroEL, which is necessary for production of active LuxR; and AinS, an acyl-HSL synthase that catalyzes the synthesis of octanoyl-HSL (VAI-2). The population density-dependent accumulation of VAI-1 triggers induction of lux operon (luxICDABEG; genes for luminescence enzymes and for LuxI) transcription and luminescence by binding to LuxR, forming a complex that facilitates the association of RNA polymerase with the luxoperon promoter. VAI-2, which apparently interferes with VAI-1 binding to LuxR, operates to limit premature luxoperon induction. Hierarchical control is imposed on the system by 3':5'-cyclic AMP (cAMP) and cAMP receptor protein (CRP), which are necessary for activated expression of luxR. Several non-lux genes in V. fischeri are controlled by LuxR and VAI-1. Quorum regulation in V. fischeri serves as a model for LuxI/LuxR-type quorum sensing systems in other gram-negative bacteria.
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PMID:Quorum regulation of luminescence in Vibrio fischeri. 1094 79

Norepinephrine induced lipolysis in rat fat cells, in vitro, in a time- and concentration-dependent manner, without concomitantly increasing hormone-sensitive lipase (HSL) activity. It also induced, time and concentration dependently, HSL translocation from the cytosol to the lipid droplets in fat cells. Isoproterenol, forskolin, dibutyryl cyclic AMP, and theophylline also induced lipolysis in fat cells, but did not stimulate HSL activity. These agents also induced HSL translocation from the cytosol to the lipid droplets in fat cells: about 80% to 90% of all HSL was located in lipid droplets after incubation for 1 h. These results suggest that the critical event in lipolytic activation of fat cells induced by lipolytic agents is not an increase in the catalytic activity of HSL but translocation of HSL to its substrate on the surfaces of lipid droplets in fat cells.-Morimoto, C., K. Kameda, T. Tsujita, and H. Okuda. Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells. J. Lipid Res. 2001. 42: 120;-127.
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PMID:Relationships between lipolysis induced by various lipolytic agents and hormone-sensitive lipase in rat fat cells. 1116 Mar 73

Hereditary factors may be involved in the pathogenesis of type 2 diabetes. A polymorphism in the hormone-sensitive lipase (HSL) gene (HSLi6) is associated with obesity and diabetes, although it is unknown whether the polymorphism is functional and thereby influences lipolysis. We genotyped 355 apparently healthy nonobese male and female subjects for the HSLi6 polymorphism. Allele 5 was found to be the most common allele (allele frequency 0.57). In 117 of the subjects, we measured abdominal subcutaneous fat cell lipolysis induced by drugs acting at various steps in the lipolytic cascade. The lipolysis rate induced by norepinephrine isoprenaline (acting on beta-adrenoceptors), forskolin (acting on adenylyl cyclase), and dibutyryl cyclic AMP (acting on HSL) were all decreased by approximately 50% in allele 5 homozygotes, as compared with noncarriers. Heterozygotes showed an intermediate lipolytic rate. The difference in lipolysis rate between genotypes was more pronounced in men than in women. We conclude that allele 5 of the HSLi6 polymorphism is associated with a marked decrease in the lipolytic rate of abdominal fat cells. This may in turn contribute to the development of obesity.
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PMID:A common hormone-sensitive lipase i6 gene polymorphism is associated with decreased human adipocyte lipolytic function. 1157 28

The influence of obesity on the lipolytic capacity of isolated sc fat cells was studied prospectively in 13 women and 10 men, all obese, but otherwise healthy, before and 2 and 3 yr after weight reduction by bariatric surgery. Nonobese subjects (25 women and 17 men) without a family history of obesity served as the control group. Lipolytic capacity was determined after stimulation at different steps of the lipolytic cascade with noradrenaline, isoprenaline, forskolin, and (Bu)(2)AMP. Bariatric surgery was followed by a marked and similar reduction of body mass index and fat cell volume (approximately 40%) in both genders. Before weight loss, lipolytic capacity per cell was elevated in obese women and decreased to normal levels after weight reduction at 2 and 3 yr. However, lipolytic capacity per fat cell surface area was not changed in obese women. In obese men, lipolytic capacity per cell was almost the same as in lean men and was not influenced by weight reduction. Lipolytic capacity was related to fat cell size in women (P = 0.0008; r = 0.58), but not in men (P = 0.67; r = 0.086). The protein content of hormone-sensitive lipase, which determines lipolytic capacity, was significantly lower in obese men and women and increased slightly after weight reduction in men only. Thus, in women, but not in men, the adipocyte lipolytic capacity is influenced by obesity and weight reduction, probably due to changes in fat cell size. These gender differences are not related to the amount of hormone-sensitive lipase protein in adipocytes.
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PMID:Major gender differences in the lipolytic capacity of abdominal subcutaneous fat cells in obesity observed before and after long-term weight reduction. 1183 18

It has been proposed that hormone-sensitive lipase (HSL) regulates intramuscular triacylglycerol hydrolysis in skeletal muscle. The primary purpose of this study was to examine the early activation of HSL and the changes in the putative intramuscular and hormonal regulators of HSL activity at various aerobic exercise intensities. Eight male subjects cycled for 10 min at power outputs corresponding to 30, 60 and 90 % peak oxygen uptake (VO(2,peak)). Muscle samples were obtained at rest and following 1 and 10 min of exercise. Intramuscular triacylglycerol (mean +/- S.E.M.: 24.3 +/- 2.3 mmol (kg dry mass (DM))(-1)), long-chain fatty acyl CoA (13.9 +/- 1.4 micromol (kg DM)(-1)) and HSL activity (1.87 +/- 0.07 mmol min(-1) (kg DM)(-1))) were not different between trials at rest. HSL activity increased at 1 min of exercise at 30 and 60 % VO(2,peak), and to a greater extent at 90 % VO(2,peak). HSL activity remained elevated after 10 min of exercise at 30 and 60 % VO(2,peak), and decreased at 90 % VO(2,peak) from the rates observed at 1 min (1 min: 3.41 +/- 0.3 mmol min(-1) (kg DM)-1; 10 min: 2.92 +/- 0.26 mmol min(-1) (kg DM)(-1)), P < 0.05). There were no effects of exercise power output or time on long-chain fatty acyl CoA content. At 90 % VO(2,peak), skeletal muscle contents of ATP and phosphocreatine were decreased (P < 0.05), and free ADP and free AMP were increased (P < 0.05) during exercise. No changes in these metabolites occurred at 30 % VO(2,peak) and only modest changes were observed at 60 % VO(2,peak). Plasma adrenaline increased (P < 0.05) during exercise at 90 % VO(2,peak) only. These data suggest that a factor related to the onset of exercise (e.g. Ca2+) activates HSL early in exercise. Given the activation of HSL early in exercise, at a time when intramuscular triacylglycerol hydrolysis and fat oxidation are considered to be negligible, we propose that the control of intramuscular triacylglycerol hydrolysis is not solely related to the level of HSL activation, but must also be regulated by postactivational factors.
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PMID:Effects of dynamic exercise intensity on the activation of hormone-sensitive lipase in human skeletal muscle. 1256 95

We investigated the effect of increased plasma adrenaline on hormone-sensitive lipase (HSL) activity and extracellular regulated kinase (ERK) 1/2 phosphorylation during exercise. Seven untrained men rested for 20 min and exercised for 10 min at 60 % peak pulmonary oxygen uptake on three occasions: with adrenaline infusion throughout rest and exercise (ADR), with no adrenaline infusion (CON) and with adrenaline infusion commencing after 3 min of exercise (EX+ADR). Muscle samples were obtained at rest before (Pre, -20 min) and after (0 min) infusion, and at 3 and 10 min of cycling. Exogenous adrenaline infusion increased (P < 0.05) plasma adrenaline at rest during ADR, which resulted in greater HSL activity (Pre, 2.14 +/- 0.10 mmol min-1 (kg dry matter (dm))-1; 0 min, 2.74 +/- 0.20 mmol min-1 (kg dm)-1). Subsequent exercise had no effect on HSL activity. During exercise in CON, HSL activity was increased (P < 0.05) above rest at 3 min but was not increased further by 10 min. The infusion of exogenous adrenaline at 3 min of exercise in EX+ADR resulted in a marked elevation in plasma adrenaline levels (3 min, 0.57 +/- 0.12 nM; 10 min, 10.08 +/- 0.84 nM) and increased HSL activity by 25 %. HSL activity at 10 min was greater (P < 0.05) in EX+ADR compared with CON. There were no changes between trials in the plasma concentrations of insulin and free fatty acids (FFA) and the muscle contents of free AMP, all putative regulators of HSL activity. ERK1/2 phosphorylation increased at 3 min in CON and EX+ADR. Because HSL activity did not increase during exercise when adrenaline was infused prior to exercise (ADR) and because HSL activity increased when adrenaline was infused during exercise (EX+ADR), we conclude that (1) high adrenaline levels can stimulate HSL activity regardless of the metabolic milieu and (2) large increases in adrenaline during exercise, independent of changes in other putative regulators, are able to further stimulate the contraction-induced increase in HSL activity. The results also demonstrate that increased ERK 1/2 phosphorylation coincides with elevated HSL activity, indicating that ERK 1/2 may mediate the contraction-induced increase in HSL activity early in exercise.
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PMID:Effects of plasma adrenaline on hormone-sensitive lipase at rest and during moderate exercise in human skeletal muscle. 1273 Mar 34

Cyclopiazonic acid (CPA) is a sarcoplasmic reticulum Ca2+-ATPase inhibitor that increases intracellular calcium. The role of CPA in regulating the oxidation and esterification of palmitate, the hydrolysis of intramuscular lipids, and the activation of hormone-sensitive lipase (HSL) was examined in isolated rat soleus muscles at rest. CPA (40 micro M) was added to the incubation medium to levels that resulted in subcontraction increases in muscle tension, and lipid metabolism was monitored using the previously described pulse-chase procedure. CPA did not alter the cellular energy state, as reflected by similar muscle contents of ATP, phosphocreatine, free AMP, and free ADP. CPA increased total palmitate uptake into soleus muscle (11%, P < 0.05) and was without effect on palmitate oxidation. This resulted in greater esterification of exogenous palmitate into the triacylglycerol (18%, P < 0.05) and phospholipid (89%, P < 0.05) pools. CPA decreased (P < 0.05) intramuscular lipid hydrolysis, and this occurred as a result of reduced HSL activity (20%, P < 0.05). Incubation of muscles with 3 mM caffeine, which is also known to increase Ca2+ without affecting the cellular energy state, reduced HSL activity (24%, P < 0.05). KN-93, a calcium/calmodulin-dependent kinase inhibitor (CaMKII), blocked the effects of CPA and caffeine, and HSL activity returned to preincubation values. The results of the present study demonstrate that CPA simultaneously decreases intramuscular triacylglycerol (IMTG) hydrolysis and promotes lipid storage in isolated, intact soleus muscle. The decreased IMTG hydrolysis is likely mediated by reduced HSL activity, possibly via the CaMKII pathway. These responses are not consistent with the increased hydrolysis and decreased esterification observed in contracting muscle when substrate availability and the hormonal milieu are tightly controlled. It is possible that more powerful signals or a higher [Ca2+] may override the lipid-storage effect of the CPA-mediated effects during muscular contractions.
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PMID:Hormone-sensitive lipase activity and triacylglycerol hydrolysis are decreased in rat soleus muscle by cyclopiazonic acid. 1275 19

Successful adaptation to starvation in mammals depends heavily on the regulated mobilization of fatty acids from triacylglycerols stored in adipose tissue. Although it has long been recognized that cyclic AMP represents the critical second messenger and hormone-sensitive lipase (HSL)**Abbreviations used in this paper: ADRP, adipocyte differentiation-related protein; HSL, hormone-sensitive lipase; PKA, protein kinase A; TAG, triacylglycerol. the rate-determining enzyme for lipolysis, simple activation of the enzyme has failed to account for the robust augmentation of fatty release in response to physiological agonists. In this issue, Sztalryd et al. (2003) provide convincing support to the notion that the subcellular compartmentalization of lipase also regulates lipolysis, and, more importantly, that proteins other than HSL are localized to the lipid droplet and are indispensable for its optimal hydrolysis.
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PMID:Lipolysis: more than just a lipase. 1281 Jun 97


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