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)

In intact rat adipocytes hormone-sensitive lipase has been shown to be phosphorylated on serine residues in two different phosphorylation sites: a regulatory site phosphorylated by cyclic AMP-dependent protein kinase and a basal site, which does not directly affect the enzyme activity, phosphorylated by cyclic AMP-independent protein kinase(s) [(1984) Proc. Natl. Acad. Sci. USA 81, 3317-3321]. Cyclic GMP-dependent protein kinase catalyzed the phosphorylation of the same two phosphorylation sites on the isolated enzyme, at serine residues. Both sites were phosphorylated at about the same rate, with the hormone-sensitive lipase activity concomitantly enhanced.
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PMID:Phosphorylation of hormone-sensitive lipase by cyclic GMP-dependent protein kinase. 298 24

To explore the role of calmodulin (CaM) in lipolysis, studies were carried out on effects of CaM inhibitors on hormone-stimulated lipolysis, the activity of cAMP-dependent protein kinase, and phosphorylation of endogenous substrate proteins. When adipocytes were incubated with trifluoperazine (TFP) and W-7 but not with W-5, stimulation of lipolysis by epinephrine was blunted. W-7 also inhibited lipolysis induced by ACTH, 1-methyl-3-isobutylxanthine (MIX) or (Bu)2 cAMP. The binding of 3H-cAMP to its receptor protein (the regulatory subunit of protein kinase) as well as the activity of cAMP-dependent protein kinase was suppressed by W-7, and the anti-CaM antibody, but not by W-5. The CaM-dependence of the protein kinase was also proved by the fact that the protein kinase activity that was markedly reduced in CaM-depleted cell extracts, was significantly restored by addition of exogenous CaM to them. Furthermore, W-7 decreased cAMP-stimulated phosphorylation of endogenous substrate proteins (mol wt 230k, 200k, 130k, 85k, 75k, and 50kdalton), among which the one of 85kdalton is most likely to be the hormone-sensitive lipase. These findings suggest that CaM is involved in the mechanism of hormone-induced lipolysis by exerting stimulatory effects on the activation of cAMP-dependent protein kinase in cell extracts capable of phosphorylating substrate proteins including hormone-sensitive lipase.
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PMID:The role of calmodulin in hormone-stimulated lipolysis. 298 17

Exposure of 3T3-L1 adipocytes to 1 nM insulin for 10 min results in activation of particulate cAMP phosphodiesterase and suppression of lipolysis stimulated by 10 nM isoproterenol. When lipolysis was increased by cilostamide, a selective inhibitor of the particulate phosphodiesterase, the antilipolytic effect of insulin was not observed. Insulin did suppress lipolysis stimulated by Ro 20-1724, an inhibitor of soluble cAMP phosphodiesterase activity. Cilostamide did not interfere with insulin stimulation of glucose uptake, nor did it have any direct effect on cAMP-dependent protein kinase. Thus, inhibition of particulate but not soluble cAMP phosphodiesterase blocked the antilipolytic effect of insulin. Our findings support the idea that insulin inhibits lipolysis, perhaps in large part by activating particulate "low Km" cAMP phosphodiesterase, which seems to be functionally closely coupled with the hormone-sensitive lipase-regulatory system influencing primarily a pool of cAMP utilized by the relevant protein kinase.
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PMID:Antilipolytic action of insulin: role of cAMP phosphodiesterase activation. 298 73

The activity of a pigeon adipose tissue hormone-sensitive triacylglycerol lipase preparation was increased from 2- to 5-fold by the presence of phosphatidylethanolamine in assays with three different methods of preparing triolein substrates. Phosphatidylethanolamine from egg yolk produced the greatest stimulation of lipase activity; the stimulation was concentration-dependent but was not time-dependent. A comparable increase in triacylglycerol lipase activity due to phosphatidylethanolamine was also observed with enzyme preparations from chicken and rat adipose tissue. Phosphatidylcholine, phosphatidylserine, phosphatidylinositol, phosphatidic acid, cardiolipin, sphingomyelin, Triton X-100 and sodium dodecyl sulfate all inhibited enzyme activity. Phosphatidylethanolamine had no effect on acid lipase activity in the pigeon adipose tissue preparation. Preincubation of the pigeon adipose tissue lipase with ATP, cyclic AMP and protein kinase resulted in a 2.15-fold activation of hydrolase activity determined in the absence of phosphatidylethanolamine. In contrast, non-activated and protein kinase-activated forms of the lipase were characterized as having very nearly the same activity in assays with substrate preparations containing phosphatidylethanolamine. The phosphatidylethanolamine-dependent stimulation of lipase activity was characterized kinetically as being due to an increase in maximal velocity. The modulation of the adipose tissue hormone-sensitive lipase activity by phospholipids could be involved in the hormonal regulation of lipolysis.
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PMID:Stimulation of the hormone-sensitive triacylglycerol lipase from adipose tissue by phosphatidylethanolamine. 298 22

Lipolysis of intracellular triglycerides in the heart has been shown to be regulated by hormones. However, activation of myocardial triglyceride lipase in a cell-free system has not been directly demonstrated. In the present studies, initial attempts to demonstrate cAMP-dependent activation of triglyceride lipase using the 1,000 X g supernatant fraction (S1) of mouse heart homogenate were unsuccessful, presumably due to the masking effects of high levels of lipoprotein lipase activity even when assayed at pH 7.4 and in the absence of apolipoprotein C-II. Myocardial lipoprotein lipase in the 40,000 X g supernatant fraction was then removed by heparin-Sepharose affinity chromatography. The lipoprotein lipase-free fractions were shown to contain neutral triglyceride lipase and neutral cholesterol esterase of about equal activities. The triglyceride lipase and cholesterol esterase activities fell progressively during preincubation in the presence of 5 mM Mg2+. Additions of cAMP and ATP resulted in 40-70% activation of both triglyceride lipase and cholesterol esterase. The activation was blocked by protein kinase inhibitor and was restored by the addition of exogenous cAMP-dependent protein kinase. Since lipoprotein lipase has no activity toward cholesteryl oleate, activation of cholesterol esterase in untreated S1 was readily demonstrable. Both triglyceride lipase and cholesterol esterase activities were present in homogenates prepared from isolated rat heart myocytes. We conclude that the myocardium contains a hormone-sensitive lipase that is regulated in a fashion similar to that of the adipose tissue enzyme.
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PMID:Activation of myocardial neutral triglyceride lipase and neutral cholesterol esterase by cAMP-dependent protein kinase. 298 7

Swine adipose tissue hormone-sensitive lipase, purified 475-fold to 10% protein purity, has been identified as a polypeptide of Mr = 84,000. The enzyme has high specific activity against tri-, di- and monoacylglycerols, as well as cholesterol esters, and is inhibited by millimolar NaF, and micromolar HgCl2 and DFP. The enzyme polypeptide serves as a substrate for cyclic AMP-dependent protein kinase. The characteristics of the hormone-sensitive lipase from swine adipose tissue are similar to those reported previously for the enzyme from rat. They differ from those reported for the lipase from chicken adipose tissue, and possible reasons for these differences are discussed.
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PMID:Hormone-sensitive lipase from swine adipose tissue: identification and some properties. 298 58

The fast-acting lipolytic hormones and insulin regulate adipose tissue lipolysis through control of the activity of hormone-sensitive lipase. This enzyme catalyzes the rate limiting step of adipose tissue lipolysis--the hydrolysis of stored triacylglycerols. The isolated enzyme is rapidly phosphorylated and activated by cyclic AMP-dependent protein kinase, with 1 mol of phosphate incorporated per mol of lipase Mr = 84000 subunit into a single serine residue. The enzyme is dephosphorylated and deactivated by protein phosphatases type 1, 2A and 2C. In the intact, isolated adipocytes the enzyme incorporates phosphate in the absence of hormonal stimulation into a specific 'basal' phosphorylation site. The phosphorylation of this 'basal' site (into a serine residue) is not accompanied with any change of the activity of the enzyme and is not influenced by hormones. The fast-acting lipolytic hormones induce a phosphorylation of another serine residue in a 'regulatory' phosphorylation site, which is identical to that phosphorylated in the isolated enzyme by cyclic AMP-dependent protein kinase. Following the phosphorylation of the 'regulatory' site the activity of the lipase, and consequently the rate of lipolysis, is increased almost 50-fold. Insulin causes a rapid net dephosphorylation of the lipase and exerts its well-known anti-lipolytic action. Half-maximal inhibition of both phosphorylation and activity occurs at an insulin concentration of about 25 pM. The mechanism(s) whereby insulin causes its effects is unknown but apparently to a large extent involve reduction of the cellular cyclic AMP level.
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PMID:Molecular mechanisms for hormonal control of adipose tissue lipolysis. 299 12

Cultured rat epididymal preadipocytes exposed for 24-72 h to either bezafibrate or clofibrate added to the culture medium were extensively converted to fat-loaded adipocytes. Adipocyte conversion increased during the first 5-7 days following plating, reaching a level of 100% and 60% conversion with bezafibrate and clofibrate, respectively, as compared to 10% conversion in their absence. Adipocyte conversion in culture was a saturable function of the hypolipidemic effectors and was associated with an increase in the incorporation rate of exogenous palmitate into triacylglycerols, in glycerol-3-phosphate dehydrogenase and hormone-sensitive lipase activities but not in lipoprotein lipase activity. Adipocyte conversion by hypolipidemic drugs was much more prominent than that exerted by dibutyryl cAMP, and the relative conversion efficiency of the two fibrate drugs did not correlate with their respective cAMP content of the culture. Hence, hypolipidemic drugs and dibutyryl cAMP appear to act independently in initiating adipose conversion in primary epididymal preadipocytes.
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PMID:Adipose conversion of cultured rat primary preadipocytes by hypolipidemic drugs. 301 19

The objective of this work was to examine the mechanism by which dietary saturated fatty acids, as compared with polyunsaturated fatty acids, lower hormone-sensitive lipolysis in rat adipocytes. Rats were fed a purified diet containing 14% of a fat with a high concentration of either saturated fatty acids (coconut oil or beef fat) or polyunsaturated fatty acids (safflower oil) as a control. In addition, each diet contained 2% corn oil. The animals were fed these diets for 4 wk. Norepinephrine-stimulated lipolysis was 50% lower when diets rich in saturated fatty acids, regardless of their chain length, were fed than when a diet containing a high concentration of polyunsaturated fatty acids was fed. The specific activities of adenylate cyclase, 3',5'-cyclic nucleotide (cAMP) phosphodiesterase and hormone-sensitive lipase were lower when saturated fatty acids were fed than when polyunsaturated fatty acids were fed. Accumulation of cAMP upon stimulation with 10(-5) M norepinephrine was lower when saturated fatty acids were fed than when polyunsaturated fatty acids were fed. Moreover, adipocytes were larger when saturated fatty acids were fed than when polyunsaturated fatty acids were fed. The data obtained suggest that dietary saturated fats exert their inhibitory effect on hormone-stimulated lipolysis by influencing several points in the lipolytic cascade.
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PMID:Effect of dietary saturated fatty acids on hormone-sensitive lipolysis in rat adipocytes. 301 93

The effect of interleukin-1 and interleukin-2 on lipolysis and the adrenergic control of lipolysis was studied. Biopsy specimens of human adipose tissue were incubated in media containing 3H-palmitate and 14C-glucose, and the ratio of these isotopes was used to determine adipocyte lipolysis. Isoproterenol, clonidine, and theophylline were used in the media to stimulate the beta 1- and alpha 2-receptors and the subreceptor mechanism, respectively. Interleukin-1 had no effect on basal lipolysis, and at maximal receptor stimulation, it had no effect on the adrenergic receptor control of lipolysis. Interleukin-2 had no effect on basal lipolysis or on the beta-adrenergic receptor. Interleukin-2 significantly (p less than 0.02) decreased the alpha 2-inhibition of lipolysis by 68%. The effect of interleukin-2 on the alpha-receptor was demonstrated to be a significant 45% decrease (p less than 0.03) in the receptor responsiveness (a measure of the postreceptor mechanism) with no alteration in receptor sensitivity (a measure of receptor number). This data suggest that interleukin-2 stimulates lipolysis by decreasing the alpha 2-adrenergic inhibition of hormone-sensitive lipase.
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PMID:The effect of interleukin-1 and interleukin-2 on the adrenergic control of hormone-sensitive lipase in the human adipocyte. 301 34


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