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)

These trials explored metabolic events associated with monensin-induced changes in milk composition. In trial 1, diets containing 0 or 33 ppm monensin sodium were fed ad libitum to separate groups of 7 mature lactating goats. In trial 2, diets containing 0 or 18 ppm monensin sodium were fed ad libitum to two groups with 5 mature (greater than 2 yr) and seven young (less than 2 yr) lactating does in each group. Blood was sampled at 1200 h and at 3 min after morning milking in both trials. Diets containing 33 ppm monensin increased serum growth hormone and plasma glucagon. Monensin (33 ppm) increased growth hormone from 13 to 60 ng/ml in samples taken 3 min after milking. Monensin (33 ppm) decreased insulin in these postmilking samples from 432 to 317 pg/ml but increased midday insulin in the samples taken between milkings from 279 to 349 pg/ml. Monensin did not affect plasma glucose or serum prolactin concentrations. Monensin fed at 18 ppm did not affect growth hormone, glucagon, adipose acetyl CoA carboxylase activity, hormone-sensitive lipase, or glucose concentrations. Young animals had higher growth hormone, glucose, and glucagon than mature does. The results indicate that effects of milk production intensity can be more important than monensin treatment on milk composition and circulating hormone concentrations.
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PMID:Effects of feeding monensin to lactating goats: acetyl coenzyme A carboxylase, hormone-sensitive lipase, plasma glucose, and circulating hormones. 288 43

The phosphorylation of cytosolic and plasma membrane proteins was studied in isolated fat cells from euthyroid and thyroidectomized rats. The analysis, by sodium dodecyl sulphate-polyacrylamide gel electrophoresis, of subcellular fractions of 32P-labelled fat cells revealed the presence of 10-12 phosphoprotein bands in the cytosol. The washed plasma membrane fraction contained 4 major phosphoproteins with estimated molecular weights of 70-67, 60, 42-40 and 26-22 kDa. Two-dimensional analysis of the 32P-labelled phosphoproteins showed that their isoelectric points were between 6.3 and 4.1. The profiles and the isoelectric points were similar in fat cells from euthyroid and thyroidectomized rats. The state of hypothyroidism did not affect the basal phosphorylation of fat cell proteins of the cytosolic or plasma membrane fractions. The incubation of fat cells from euthyroid rats in the presence of isoproterenol or dibutyryl adenosine cyclic monophosphate led to (a) an increase in the 32P labelling of cytosolic proteins which may be subunits of acetyl CoA carboxylase, ATP citrate lyase, hormone-sensitive lipase and other proteins, with apparent molecular weights between 50 and 42 kDa, and (b) an increase in the 32P labelling of plasma membrane proteins of 26-22 kDa. In the case of fat cells from hypothyroid rats, the dibutyryl adenosine cyclic monophosphate increased the 32P labelling of plasma membrane proteins, whereas in the presence of isoproterenol these reactions did not occur. These results show that thyroid hormones control the 32P labelling of proteins of the cytosol and plasma membrane fractions of rat fat cells and therefore, at least in some cases, the lipolytic and lipogenic pathways.
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PMID:Thyroid hormones and fat cell phosphorylation. 609 86

The effects of free fatty acids and fatty acyl esters of coenzyme A and carnitine on the activity of a hormone-sensitive lipase preparation made from pigeon adipose tissue were determined. Oleic acid (100 microM) resulted in a 40% inhibition of lipase activity. A more potent inhibition of lipase activity was seen with long-chain fatty acyl CoA compounds. The concentration required for half-maximal inhibition with oleoyl CoA and palmitoyl CoA was 25-40 microM, whereas palmitoyl carnitine stimulated lipase activity. Activated lipase preparations (preincubated with Mg2+, ATP, cyclic AMP and protein kinase) were 4-6 times more sensitive to inhibition by oleoyl CoA than were nonactivated preparations. An increase in cellular levels of fatty acyl coenzyme A could, therefore, contribute to the feedback inhibition of lipolysis in adipose tissue.
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PMID:Inhibition of the hormone-sensitive lipase in adipose tissue by long-chain fatty acyl coenzyme A. 632 7

The review examines the mechanisms regulating the activities of the two key enzymes determining rates of glucose and fatty acid oxidation, i.e., the pyruvate dehydrogenase (PDH) complex and the carnitine palmitoyltransferase (CPT) system. The review also evaluates the regulatory importance of gene expression in the control of tissue fuel selection within the context of substrate competition between glucose and fatty acids. It identifies a strong indirect input of nutrient-gene interactions in the control of pyruvate oxidation through the regulated provision of pyruvate as a substrate for PDH and as an inhibitor of PDH kinase. Nutrient-gene interactions are also identified in relation to the regulation of CPT I activity by malonyl-CoA (inhibitor) and by the provision of long-chain acyl-CoA (substrate/activator), the latter via the hydrolysis of plasma or tissue triacylglycerol (by lipoprotein lipase and hormone-sensitive lipase, respectively). We discuss how such regulation is reinforced by long-term modulation of PDH kinase-specific activity and CPT I maximal activity. We also explore the role of mechanisms operating at the levels of the PDH complex and the CPT system that act to promote and accelerate a switch in fuel utilization once a committed change in nutrient supply has been established. In particular, we discuss the regulatory influences exerted by altered sensitivities of PDH kinase to inhibition by pyruvate and CPT I to inhibition by malonyl-CoA, respectively.
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PMID:Interactive regulation of the pyruvate dehydrogenase complex and the carnitine palmitoyltransferase system. 829 90

Triglycerides in the beta-cell may be important for stimulus-secretion coupling, through provision of a lipid-derived signal, and for pathogenetic events in NIDDM, where lipids may adversely affect beta-cell function. In adipose tissues, hormone-sensitive lipase (HSL) is rate-limiting in triglyceride hydrolysis. Here, we investigated whether this enzyme is also expressed and active in beta-cells. Northern blot analysis and reverse transcription-polymerase chain reaction demonstrated that HSL is expressed in rat islets and in the clonal beta-cell lines INS-1, RINm5F, and HIT-T15. Western blot analysis identified HSL in mouse and rat islets and the clonal beta-cells. In mouse and rat, immunocytochemistry showed a predominant occurrence of HSL in beta-cells, with a presumed cytoplasmic localization. Lipase activity in homogenates of the rodent islets and clonal beta-cells constituted 2.1 +/- 0.6% of that in adipocytes; this activity was immunoinhibited by use of antibodies to HSL. The established HSL expression and activity in beta-cells offer a mechanism whereby lipids are mobilized from intracellular stores. Because HSL in adipocytes is activated by cAMP-dependent protein kinase (PKA), PKA-regulated triglyceride hydrolysis in beta-cells may participate in the regulation of insulin secretion, possibly by providing a lipid-derived signal, e.g., long-chain acyl-CoA and diacylglycerol.
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PMID:Hormone-sensitive lipase, the rate-limiting enzyme in triglyceride hydrolysis, is expressed and active in beta-cells. 989 50

A lipolytic domain (AOD9401) of human growth hormone (hGH) which resides in the carboxyl terminus of the molecule and contains the amino acid residues 177-191, has been synthesized using solid-phase peptide synthesis techniques. AOD9401 stimulated hormone-sensitive lipase and inhibited acetyl coenzyme A carboxylase (acetyl CoA carboxylase) in isolated rat adipose tissues, in a similar manner to the actions of the intact hGH molecule. The synthetic lipolytic domain mimicked the effect of the intact growth hormone on diacylglycerol release in adipocytes. Chronic treatment of obese Zucker rats with AOD9401 for 20 days reduced the body weight gain of the animals, and the average cell size of the adipocytes of the treated animals decreased from 110 to 80 microm in diameter. Unlike hGH, synthetic AOD9401 did not induce insulin resistance or glucose intolerance in the laboratory animals after chronic treatment. The results suggest that AOD9401 has the potential to be developed into a therapeutic agent for the control of obesity.
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PMID:Molecular and cellular actions of a structural domain of human growth hormone (AOD9401) on lipid metabolism in Zucker fatty rats. 1111 8

Endogenous lipid stores are thought to be involved in the mechanism whereby the beta-cell adapts its secretory capacity in obesity and diabetes. In addition, hormone-sensitive lipase (HSL) is expressed in beta-cells and may provide fatty acids necessary for the generation of coupling factors linking glucose metabolism to insulin release. We have recently created HSL-deficient mice that were used to directly assess the role of HSL in insulin secretion and action. HSL(-/-) mice were normoglycemic and normoinsulinemic under basal conditions, but showed an approximately 30% reduction of circulating free fatty acids (FFAs) with respect to control and heterozygous animals after an overnight fast. An intraperitoneal glucose tolerance test revealed that HSL-null mice were glucose-intolerant and displayed a lack of a rise in plasma insulin after a glucose challenge. Examination of plasma glucose during an insulin tolerance test suggested that HSL-null mice were insulin-resistant, because plasma glucose was barely lowered after the injection of insulin. Freshly isolated islets from HSL-deficient mice displayed elevated secretion at low (3 mmol/l) glucose, failed to release insulin in response to high (20 mmol/l) glucose, but had a normal secretion when challenged with elevated KCl. The phenotype of heterozygous mice with respect to the measured parameters in vitro was similar to that of wild type. Finally, the islet triglyceride content of HSL(-/-) mice was 2-2.5 fold that in HSL(-/+) and HSL(+/+) animals. The results demonstrate an important role of HSL and endogenous beta-cell lipolysis in the coupling mechanism of glucose-stimulated insulin secretion. The data also provide direct support for the concept that some lipid molecule(s), such as FFAs, fatty acyl-CoA or their derivatives, are implicated in beta-cell glucose signaling.
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PMID:A role for hormone-sensitive lipase in glucose-stimulated insulin secretion: a study in hormone-sensitive lipase-deficient mice. 1152 61

Leptin acutely increases fatty acid (FA) oxidation and triacylglycerol (TG) hydrolysis and decreases TG esterification in oxidative rodent muscle. However, the effects of chronic leptin administration on FA metabolism in skeletal muscle have not been examined. We hypothesized that chronic leptin treatment would enhance TG hydrolysis as well as the capacity to oxidize FA in soleus (SOL) muscle. Female Sprague-Dawley rats were infused for 2 wk with leptin (LEPT; 0.5 mg x kg(-1) x day(-1)) by use of subcutaneously implanted miniosmotic pumps. Control (AD-S) and pair-fed (PF-S) animals received saline-filled implants. Subsequently, FA metabolism was monitored for 45 min in isolated, resting, and contracting (20 tetani/min) SOL muscles by means of pulse-chase procedures. Food intake (-33 +/- 2%, P < 0.01) and body mass (-12.5 +/- 4%, P = 0.01) were reduced in both LEPT and PF-S animals. Leptin levels were elevated (+418 +/- 7%, P < 0.001) in treated animals but reduced in PF-S animals (-73 +/- 8%, P < 0.05) relative to controls. At rest, TG hydrolysis was increased in leptin-treated rats (1.8 +/- 2.2, AD-S vs. 23.5 +/- 8.1 nmol/g wet wt, LEPT; P < 0.001). In contracting SOL muscles, TG hydrolysis (1.5 +/- 0.6, AD-S vs. 3.6 +/- 1.0 micromol/g wet wt, LEPT; P = 0.02) and palmitate oxidation (18.3 +/- 6.7, AD-S vs. 45.7 +/- 9.9 nmol/g wet wt, LEPT; P < 0.05) were both significantly increased by leptin treatment. Chronic leptin treatment had no effect on TG esterification either at rest or during contraction. Markers of overall (citrate synthase) and FA (hydroxyacyl-CoA dehydrogenase) oxidative capacity were unchanged with leptin treatment. Protein expression of hormone-sensitive lipase (HSL) was also unaltered following leptin treatment. Thus leptin-induced increases in lipolysis are likely due to HSL activation (i.e., phosphorylation). Increased FA oxidation secondary to chronic leptin treatment is not due to an enhanced oxidative capacity and may be a result of enhanced flux into the mitochondrion (i.e., carnitine palmitoyltransferase I regulation) or electron transport uncoupling (i.e., uncoupling protein-3 expression).
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PMID:Fatty acid oxidation and triacylglycerol hydrolysis are enhanced after chronic leptin treatment in rats. 1183 62

Insulin resistance, obesity, and diabetes are characterized by hyperglycemia, hyperinsulinemia, and hyperleptinemia and are associated with increased risk of atherosclerosis. In an effort to understand how this occurs, we have investigated whether these factors cause disregulation of cholesterol ester metabolism in J774.2 macrophages. Raising glucose levels alone was sufficient to increase uptake of acetylated low density lipoprotein but did not stimulate synthesis of cholesterol esters. In the presence of high glucose, both insulin and leptin increased the rate of cholesterol ester synthesis, although they did not further increase uptake of acetylated low density lipoprotein. However, in the presence of high glucose both insulin and leptin caused a significant increase in the activity of acyl-CoA: cholesterol O-acyltransferase (ACAT) combined with a significant reduction in the level of hormone-sensitive lipase (HSL). Because ACAT is the main enzyme responsible for cholesterol ester synthesis and HSL contributes significantly to neutral cholesterol ester hydrolase activity, this suggests that glucose primes the J774.2 cells so that in the presence of high insulin or leptin they will store cholesterol esters. This contrasts with 3T3-L1 adipocytes, where HSL activity and expression are increased by insulin in high glucose conditions. These findings may provide an explanation for the observation that in conditions characterized by hyperglycemia, hyperleptinemia, and hyperinsulinemia, triglyceride lipolysis in adipocytes is increased while hydrolysis of cholesterol esters in macrophages is decreased, contributing to foam cell formation.
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PMID:Glucose-dependent regulation of cholesterol ester metabolism in macrophages by insulin and leptin. 1220 Apr 16

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


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