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)

Prospective clinical studies have shown that hypotension from hemorrhage contributes to increased morbidity and mortality in patients with traumatic brain injury. It is implied that poorer outcome is the result of secondary brain injury from impaired cerebral oxygen delivery (cO2del). We studied the early and late effects of hypertonic sodium lactate (HSL: 500 mOsm/L) resuscitation on mean arterial pressure (MAP), cardiac output (CO), systemic oxygen delivery (sO2del), cerebral perfusion pressure (CPP), intracranial pressure (ICP), cO2del, cerebral blood flow (CBF), serum osmolality, and cortical water content (CWC) in a porcine model of hemorrhagic shock. Swine were randomized to receive a bolus (4 mL/kg) of either lactated Ringer's solution (LR: 274 mOsm/L) or HSL after shock, followed by either LR or HSL to return MAP to baseline levels. Shed blood was returned 1 hour after resuscitation, and all animals were studied for 24 hours. Control animals were instrumented only. The HSL resuscitation significantly increased cO2del and CBF for 24 hours postresuscitation when compared with LR. The ICP in the HSL-treated animals was significantly lower throughout the postresuscitation phase when compared with the LR-treated animals (p less than 0.05). The CWC was significantly lower in the HSL-treated animals (p less than 0.05). We attribute these effects to hypertonic dehydration of both the brain parenchyma and the cerebrovascular endothelium. These data suggest that by decreasing ICP and improving cO2del after shock, HSL could decrease secondary brain injury when brain injury and shock occur together.
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PMID:Hypertonic fluid resuscitation improves cerebral oxygen delivery and reduces intracranial pressure after hemorrhagic shock. 174 30

The possibility that postprandial hyperinsulinemia could play a role in the development of hepatic lipid disturbances during convalescence from influenza B infection was explored in the ferret as a possible model of the steatosis of Reye's syndrome. Postprandial hyperinsulinemia was produced by feeding young ferrets glucose/water and a regular diet (glucose-treated group), as reflected by the mean serum insulin levels attained, which were 57 and 135 microU/ml during control and postinfluenza periods, respectively. By comparison, ferrets fed water and a regular diet (untreated group) had mean insulin levels of 19 and 22 microU/ml, while postprandial glucose levels were comparable in the two groups of animals for each period. In contrast to untreated animals, grossly visible fatty livers were found in glucose-treated ferrets during convalescence. The total lipid content of these livers had doubled compared with preinfection samples and compared with livers of untreated ferrets. By electron microscopy hepatic mitochondria showed striking changes with diminution of matrix density and reduction in cristae surface area only in convalescent samples from glucose-treated animals. Serum free fatty acid (FFA) levels were considerably higher in the glucose-treated animals during fasting before influenza and also after feeding during convalescence. Serum triglyceride (TG) levels were also high during convalescence in the glucose-treated group. Adipose tissue lipoprotein lipase activities were similar between groups, but hormone-sensitive lipase activity was twelvefold higher in glucose-treated ferrets before and after influenza B. These findings indicate that for a given stimulus, glucose-treated ferrets would mobilize more FFA than untreated ferrets. The total capacity for beta-oxidation of FA by the mitochondrial pathway was identical in all groups of animals. Total carnitine palmitoyl transferase (CPT) activity was the same in both control groups, but was significantly diminished in glucose-treated animals during convalescence. As CPT regulates the entry of FA into the mitochondrial matrix, its reduction in response to higher insulin concentrations would limit the oxidation of FA and stimulate TG accumulation. Therefore, the accumulation of lipid in the liver in this model is regarded to have been caused by the simultaneous occurrence of increased lipolysis and increased hepatic TG synthesis owing, in part, to diversion of activated FA by CPT, which is reduced in activity due to the regulatory action of insulin. These findings may have pathophysiologic relevance for the lipid changes that occur in Reye's syndrome and to fatty liver formation in hyperinsulinemic states.
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PMID:Hepatic steatosis during convalescence from influenza B infection in ferrets with postprandial hyperinsulinemia. 220 96

The "esterase" activity of hormone-sensitive lipase (HSL) was studied using water-soluble p-nitrophenyl butyrate (PNPB) as a substrate. Bovine adipose tissue HSL was purified to near homogeneity by precipitation at pH 5.0, followed by chromatography on DEAE-cellulose, phenyl-Sepharose, and high performance ion-exchange columns on Mono Q and Mono S. The purified preparation hydrolyzed emulsified triolein and cholesteryl oleate (CO), and water-soluble PNPB. In the two last steps of purification, the elution profile of the CO-hydrolyzing activity coincided with that of PNPB-hydrolyzing activity. The HSL was adsorbed to heparin-Sepharose and the CO- and PNPB-hydrolyzing activities were eluted together in the same peak. Diisopropylfluorophosphate (DFP) strongly inhibited the HSL activities and the inhibition profiles of the triolein-; CO-, and PNPB-hydrolyzing activities were essentially identical. Only one polypeptide of Mr 84,000 in partial purified HSL fraction was labeled by affinity labeling with [3H]DFP. On digestion of the enzyme with trypsin, the triolein- and CO-hydrolyzing activities were lost more rapidly than the PNPB-hydrolyzing activity. Phosphorylation increased the triolein-hydrolyzing activity to 40% more than that of the control, but did not affect the CO- and PNPB-hydrolyzing activities.
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PMID:p-nitrophenyl butyrate hydrolyzing activity of hormone-sensitive lipase from bovine adipose tissue. 279 98

To determine the safety and efficacy of a hypertonic solution for hypovolemic resuscitation, we compared the acute and delayed effects of hypertonic sodium lactate solution (514 mOsm) to Ringer's lactate solution (274 mOsm) in a porcine model of hemorrhagic shock. Cardiovascular, pulmonary, renal, and cerebral functions were examined in mature swine after their blood volume had been reduced by 40%. Hemorrhage produced significant decreases in blood pressure, cardiac output, and creatinine clearance, which were reversed with resuscitation. Resuscitation with Ringer's lactate solution required significantly more fluid and produced a significantly greater increase in intracranial pressure than did hypertonic sodium lactate solution. HSL produced significant increases in serum sodium and osmolality, which resolved within 48 hours. Hypernatremia and hyperosmolality were not associated with renal or cerebral dysfunction and were corrected through increased sodium excretion, free water intake, and a negative free water clearance.
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PMID:Renal, cerebral, and pulmonary effects of hypertonic resuscitation in a porcine model of hemorrhagic shock. 341 84

Female rats receiving alcohol (20%) in drinking water during lactation (AL) were compared to pair-fed animals (PF) and normal controls (C) fed ad lib. All animals were killed on the 12th day of lactation. When compared to C rats, food intake decreased in both AL and PF groups, and this effect was followed by a lower body weight and mammary gland (MG), liver, and parametrial adipose tissue weights. Mammary glands triacylglyceride concentration (TG) was much lower in PF than in AL, although in the latter, values did not reach those of C, and had higher liver TG concentration than any of the other groups. Both PF and AL rats had lower plasma TG, glycerol, and free fatty acid concentrations and higher beta-hydroxybutyrate concentration than C rats. When compared to C rats, the rate of lipogenesis in MG was higher in both PF and AL rats, whereas in liver it was higher in PF and lower in AL rats, and in adipose tissue it was higher in PF and unchanged in AL rats. The appearance of 14C lipids 4 h after oral [14]triolein in both MG and liver was lower in AL and PF rats and only lower in adipose tissue of AL rats as compared to the c rats. Lipoprotein lipase and hormone-sensitive lipase activities were lower in MG in both PF and AL rats than in C, whereas in adipose tissue the activity of lipoprotein lipase did not differ between AL and C rats and the activity of HSL was lower in the former. These findings therefore show that in spite of reduced uptake of orally administered triglycerides due to decreased LPL activity, maternal alcohol feeding during lactation in the rat preserves the mammary gland triglyceride content thanks to enhanced lipogenetic activity. On the other hand, it causes liver triglycerides accumulation, probably as a result of the decreased rate of triglycerides released into circulation, and these changes are not caused by the reduced food intake of the animals.
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PMID:Effects of ethanol intake on lipid metabolism in the lactating rat. 888 39

A psychrotrophic bacterium producing a cold-adapted lipase upon growth at low temperatures was isolated from Alaskan soil and identified as a Pseudomonas strain. The lipase gene (lipP) was cloned from the strain and sequenced. The amino acid sequence deduced from the nucleotide sequence of the gene (924 bp) corresponded to a protein of 308 amino acid residues with a molecular weight of 33,714. LipP also has consensus motifs conserved in other cold-adapted lipases, i.e., Lipase 2 from Antarctic Moraxella TA144 (G. Feller, M. Thirty, J. L. Arpigny, and C. Gerday, DNA Cell Biol. 10:381-388, 1991) and the mammalian hormone-sensitive lipase (D. Langin, H. Laurell, L. S. Holst, P. Belfrage, and C. Holm, Proc. Natl. Acad. Sci. USA 90:4897-4901, 1993): a pentapeptide, GDSAG, containing the putative active-site serine and an HG dipeptide. LipP was purified from an extract of recombinant Escherichia coli C600 cells harboring a plasmid coding for the lipP gene. The enzyme showed a 1,3-positional specificity toward triolein. p-Nitrophenyl esters of fatty acids with short to medium chains (C4 and C6) served as good substrates. The enzyme was stable between pH 6 and 9, and the optimal pH for the enzymatic hydrolysis of tributyrin was around 8. The activation energies for the hydrolysis of p-nitrophenyl butyrate and p-nitrophenyl laurate were determined to be 11.2 and 7.7 kcal/mol, respectively, in the temperature range 5 to 35 degrees C. The enzyme was unstable at temperatures higher than 45 degrees C. The Km of the enzyme for p-nitrophenyl butyrate increased with increases in the assay temperature. The enzyme was strongly inhibited by Zn2+, Cu2+, Fe3+, and Hg2+ but was not affected by phenylmethylsulfonyl fluoride and bisnitrophenyl phosphate. Various water-miscible organic solvents, such as methanol and dimethyl sulfoxide, at concentrations of 0 to 30% (vol/vol) activated the enzyme.
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PMID:A cold-adapted lipase of an Alaskan psychrotroph, Pseudomonas sp. strain B11-1: gene cloning and enzyme purification and characterization. 946 82

Salacia (S.) reticulata, a Hippocrateaceae plant distributed in Sri Lankan and Indian forests, has been used as a supplementary food in Japan to prevent obesity and diabetes. We examined the antiobesity effects of the hot water-soluble extract (SRHW) from the roots of S. reticulata using obese rat models and an in vitro study. Body weight (P = 0.07) and periuterine fat storage (P = 0.10) in female Zucker fatty rats (8-9 wk old) tended to be suppressed by oral administration of SRHW (125 mg/kg) for 27 d. Male rats fed a high fat diet were not affected by SRHW. Furthermore, SRHW inhibited porcine pancreatic lipase (PL), rat adipose tissue-derived lipoprotein lipase (LPL) and glycerophosphate dehydrogenase (GPDH) activities with 50% inhibitory concentrations (IC(50)) of 264 (95% confidence limits: 203-393) mg/L, 15 (12-18) mg/L and 54 (35-85) mg/L, respectively, but did not inhibit hormone-sensitive lipase activity in rat adipose tissue. Next, we examined the effects of polyphenols, di- and triterpenes and salacinol isolated from the roots of S. reticulata on lipid metabolizing enzymes and lipolysis. (-)-Epigallocatechin and (-)-epicatechin-(4beta-->8)-(-)-4'-O-methylepigallocatechin inhibited PL activity with IC(50) of 88 (not calculated) and 68 (26-122) mg/L, respectively. (-)-Epicatechin, 3beta, 22beta-dihydroxyolean-12-en-29-oic acid and the tannin fraction inhibited LPL activity with IC(50) of 81 (54-214), 89 (62-214) and 35 (24-62) mg/L. Only the tannin fraction inhibited GPDH activity with an IC(50) of 6.8 (3.4-10.9) mg/L. These constituents may be involved in the lipase and GPDH inhibitory activities of SRHW. On the other hand, SRHW at 100 mg/L tended to enhance lipolysis in rat adipocytes (P = 0.06). Significant lipolytic effects were exerted by mangiferin, (-)-4'-O-methylepigallocatechin and maytenfolic acid at 100 mg/L (P < 0.01). In conclusion, polyphenolic compounds may be involved in the antiobesity effects of SRHW in rats through inhibition of fat metabolizing enzymes (PL, LPL and GPDH) and enhanced lipolysis.
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PMID:Salacia reticulata and its polyphenolic constituents with lipase inhibitory and lipolytic activities have mild antiobesity effects in rats. 1209 53

We have found that the hyperthermophilic archaeon Pyrobaculum calidifontis VA1 produced a thermostable esterase. We isolated and sequenced the esterase gene (est(Pc)) from strain VA1. est(Pc) consisted of 939 bp, corresponding to 313 amino acid residues with a molecular mass of 34,354 Da. As est(Pc) showed significant identity (30%) to mammalian hormone-sensitive lipases (HSLs), esterase of P. calidifontis (Est) could be regarded as a new member of the HSL family. Activity levels of the enzyme were comparable or higher than those of previously reported enzymes not only at high temperature (6,410 U/mg at 90 degrees C), but also at ambient temperature (1,050 U/mg at 30 degrees C). The enzyme displayed extremely high thermostability and was also stable after incubation with various water-miscible organic solvents at a concentration of 80%. The enzyme also exhibited activity in the presence of organic solvents. Est of P. calidifontis showed higher hydrolytic activity towards esters with short to medium chains, with p-nitrophenyl caproate (C(6)) the best substrate among the p-nitrophenyl esters examined. As for the alcoholic moiety, the enzyme displayed esterase activity towards esters with both straight- and branched-chain alcohols. Most surprisingly, we found that this Est enzyme hydrolyzed the tertiary alcohol ester tert-butyl acetate, a feature very rare among previously reported lipolytic enzymes. The extreme stability against heat and organic solvents, along with its activity towards a tertiary alcohol ester, indicates a high potential for the Est of P. calidifontis in future applications.
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PMID:Extremely stable and versatile carboxylesterase from a hyperthermophilic archaeon. 1214 92

Adipose tissue triacylglycerols represent the main storage of a wide spectrum of fatty acids differing by molecular structure. The release of individual fatty acids from adipose tissue is selective according to carbon chain length and unsaturation degree in vitro and in vivo in animal studies and also in humans. The mechanism of selective fatty acid mobilization from white fat cells is not known. Lipolysis is widely reported to work at a lipid-water interface where only small amounts of substrate are available. A preferential hydrolysis of a small triacylglycerol fraction enriched in certain triacylglycerol molecular species at the lipid-water interface and enzymological properties of hormone-sensitive lipase could explain the selective mobilization of fatty acids from fat cells. This selectivity could affect the individual fatty acid supply to tissues.
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PMID:Selective mobilization of fatty acids from adipose tissue triacylglycerols. 1268 20

Aquaporin-7 (AQP7) is a water/glycerol transporting protein expressed in adipocyte plasma membranes. We report here remarkable age-dependent hypertrophy in adipocytes in AQP7-deficient mice. Wild type and AQP7 null mice had similar growth at 0-16 weeks as assessed by body weight; however, by 16 weeks AQP7 null mice had 3.7-fold increased body fat mass. Adipocytes from AQP7 null mice of age 16 weeks were greatly enlarged (diameter 118 mum) compared with wild type mice (39 mum). Adipocytes from AQP7 null mice also accumulated excess glycerol (251 versus 86 nmol/mg of protein) and triglycerides (3.4 versus 1.7 mumol/mg of protein). In contrast, at age 4 weeks, adipocyte volume and body fat mass were comparable in wild type and AQP7 null mice. To investigate the mechanism(s) responsible for the progressive adipocyte hypertrophy, glycerol permeability and fat metabolism were studied in adipocytes isolated from the younger mice. Plasma membrane glycerol permeability measured by [(14)C]glycerol uptake was 3-fold reduced in AQP7-deficient adipocytes. However, adipocyte lipolysis, measured by free fatty acid release and hormone-sensitive lipase activity, and lipogenesis, measured by [(14)C]glucose incorporation into triglycerides, were not affected by AQP7 deletion. These data suggest that adipocyte hypertrophy in AQP7 deficiency results from defective glycerol exit and consequent accumulation of glycerol and triglycerides. Increasing AQP7 expression/function in adipocytes may reduce adipocyte volume and fat mass in obesity.
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PMID:Progressive adipocyte hypertrophy in aquaporin-7-deficient mice: adipocyte glycerol permeability as a novel regulator of fat accumulation. 1574


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