Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.34 (lipoprotein lipase)
 7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The regulation of adipose tissue lipoprotein lipase (LPL) by feeding and fasting occurs through post-translational changes in the LPL protein. In addition, LPL activity and secretion are decreased when N-linked glycosylation is inhibited. To better understand the role of oligosaccharide processing in the development of LPL activity and in LPL secretion, primary cultures of rat adipocytes were treated with inhibitors of oligosaccharide processing. LPL catalytic activity from the heparin-releasable fraction of adipocytes was inhibited by more than 70%, with similar decreases in LPL mass, when cells were cultured for 24 h in the presence of either tunicamycin or castanospermine. On the other hand, deoxymannojirimycin (DMJ) and swainsonine had no effect on LPL activity. LPL secretion was examined after pulse-labeling cells with [35S]methionine. The appearance of 35S-labeled LPL in the medium was blocked by treatment of cells with tunicamycin and castanospermine, whereas secretion was not affected by DMJ or swainsonine. To examine the effect of oligosaccharide processing on LPL intracellular degradation, adipocytes were treated with tunicamycin, castanospermine, and DMJ and then pulse-labeled with [35S]methionine, followed by a chase with unlabeled methionine for 120 min. The unglycosylated [35S]LPL that was synthesized in the presence of tunicamycin demonstrated essentially no intracellular degradation. In the presence of castanospermine and DMJ, the half-life of newly synthesized LPL was increased to 81 and 113 min, as compared to 65 min in control cells. Thus, castanospermine-treated adipocytes demonstrated a decrease in LPL activity and secretion, suggesting that the glucosidase-mediated cleavage of terminal glucose residues from oligosaccharides is a critical step in LPL maturation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of lipoprotein lipase activity, secretion, and degradation at different sites of post-translational processing in primary cultures of rat adipocytes. 147 87

Rats were fed (for 2 or 6 wk) purified diets containing lard (LD) or menhaden oil (MO) at two levels of dietary fat, i.e., at 11.5 and 20.8% of energy in the low fat (LF) and the medium fat (MF) diets, respectively. Following the diet period, rats were sacrificed after either an overnight fast or after uninterrupted ad libitum feeding. The studies were designed to investigate the dependence of our previously reported effects of MO, i.e. the reduction of plasma free fatty acid (FFA) levels and accumulation of hepatic triacylglycerols, on the dietary fat concentration and the nutritional state of the animal at the time of sacrifice. Reductions in plasma triacylglycerol and cholesterol levels in MO-fed relative to LD-fed rats were observed under all conditions. FFA levels were consistently reduced by MO-feeding at both dietary fat concentrations, but only when blood was sampled from ad libitum fed rats. Under these conditions there was a significant positive relationship between plasma FFA and triacylglycerol concentrations. Reduction in plasma FFA levels may be an additional mechanism associated with the triacylglycerol-lowering effect of fish oil (FO). The LF and MF MO diets caused a rise in plasma glucose levels with no significant change in insulin concentration, indicating that the reduction of FFA by MO was not related to changes in insulin concentration or insulin sensitivity. The MO diets had no effect on skeletal muscle or epididymal adipose tissue lipoprotein lipase activity, demonstrating that catabolism of triacylglycerol-rich lipoproteins contributes little, if any, to the MO-dependent reductions of plasma triacylglycerol and FFA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduction in triacylglycerol levels by fish oil correlates with free fatty acid levels in ad libitum fed rats. 148 49

Incubation of cycloheximide-treated cardiac myocytes results in a time-dependent increase in cellular and heparin-releasable lipoprotein lipase (LPL) activities. N-Methyldeoxynojirimycin (1 mM) and castanospermine (100 micrograms/ml), inhibitors of glucosidases in the endoplasmic reticulum (ER), prevented the increase in cellular LPL activity. The glucosidase inhibitors did not influence the synthesis or turnover of LPL protein. Therefore activation of LPL by glycosylation in cardiac myocytes requires the trimming of glucose residues in oligosaccharide chains by glucosidases of the ER.
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PMID:Activation of lipoprotein lipase in cardiac myocytes by glycosylation requires trimming of glucose residues in the endoplasmic reticulum. 149 6

This study was designed to determine the effects of colostral fat on energy metabolism, fat oxidation and glucose homeostasis in newborn pigs maintained during the first 29h of life at thermal neutrality (34 degrees C) or in the cold (21 degrees C). Piglets were intragastric fed normal colostrum (NFC, 6% fat) or colostrum deprived of fat (LFC, less than 1% fat). A total of 21 meals of 15 to 18g colostrum/kg birthweight was given at 65- to 70-min intervals. Feeding NFC resulted in a higher amount of retained fat with the highest value being obtained in the 34 degrees C group (P less than 0.01). Fat oxidation represented 47% of the absorbed fat in NFC-fed piglets at 34 degrees C; it was 4.5 fold higher in piglets fed NFC than in those fed LFC (P less than 0.01), and 1.8 fold higher at 21 degrees C than at 34 degrees C (P less than 0.01). At both temperatures, feeding LFC resulted in a lower energy balance (P less than 0.01), whereas nitrogen balance was not affected by temperature and colostrum treatments. At 29 hours of age, rectal temperature was the lowest in piglets fed LFC at 21 degrees C (P less than 0.05). Postnatal enhancement of fat metabolism in relation to environmental and nutritional conditions was evidenced at the tissue level through an adaptation of lipoprotein lipase and cytochrome oxidase activities, especially in the red rhomboideus muscle and the liver.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Contribution of colostral fat to thermogenesis and glucose homeostasis in the newborn pig. 152 69

Seven normal weight and 10 obese women were studied to determine the relative activities of adipose tissue lipoprotein lipase (ATLPL) in the gluteal and abdominal subcutaneous adipose tissue depots, both in the fasting state and in response to a 6-hour insulin/glucose infusion. In normal weight women, fasting gluteal enzyme activity was greater than abdominal (P less than .02). In the obese group, fasting levels of ATLPL were higher in both the gluteal and abdominal depots than in the normal weight group, but similar between regions. The regulation of ATLPL by insulin/glucose was also similar between regions in each group. When both groups were considered together, there was a strong correlation between fasting ATLPL of both regions, and between the insulin responsiveness of gluteal ATLPL and abdominal ATLPL after a 6-hour infusion. Despite regional differences in fasting ATLPL in lean women, these studies indicate that the regulation of ATLPL by insulin/glucose is largely similar in at least these two subcutaneous adipose tissue depots.
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PMID:Regional similarities in the metabolic regulation of adipose tissue lipoprotein lipase. 153 43

The thiazolidinediones are a class of novel antidiabetic compounds that enhance the response of target tissues to insulin. Pioglitazone, a thiazolidinedione analog, lowers blood glucose and insulin levels in rodent models of non-insulin-dependent diabetes mellitus. We have studied the effect of pioglitazone on 3T3-L1 cells, a cell line that undergoes differentiation from a preadipocyte fibroblastic morphology to that of an adipocyte. Pioglitazone treatment of preadipocytes enhanced the insulin- or insulin-like growth factor-1 (IGF-I)-regulated differentiation (monitored by the rate of lipogenesis or triglyceride accumulation), whereas treatment of the cells in the absence of insulin or IGF-I resulted in no apparent change in the cellular phenotype. Pioglitazone caused both a leftward shift and enhanced maximum response for the IGF-I-regulated differentiation of the cells, consistent with the idea that the drug enhances the sensitivity of cells to polypeptide hormones. A series of pioglitazone analogs were tested in this system, and variations in activity relative to that of the parent compound were observed. A study of the time required for the drug to exert an effect on differentiation revealed that an increased rate of lipogenesis occurred 16-24 hr after drug treatment in appropriately staged cells. An increased rate of glucose transport and increased activity of lipogenic enzymes were noted in a time frame that correlated with the change in lipogenesis. Analysis of mRNA abundance for Glut-4, lipoprotein lipase, and glucose-6-phosphate dehydrogenase showed that pioglitazone enhanced the insulin induction of these mRNA species. Thus, pioglitazone, in combination with insulin or IGF-I, appears to be exerting effects on the cellular phenotype by eliciting changes in the expression of genes that regulate metabolic pathways leading to the acquisition of the differentiated phenotype.
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PMID:Enhancement of adipocyte differentiation by an insulin-sensitizing agent. 153 16

The relationship between maturation of lipoprotein lipase (LPL) and its translocation from the endoplasmic reticulum (ER) to the Golgi complex was determined by measuring lipolytic activity under conditions preventing transport of the enzyme from the ER to the Golgi compartment. In the presence of brefeldin A, a reagent that inhibits movement of proteins from the ER and causes the disassembly of the Golgi complex, pro-5 Chinese hamster ovary cells accumulated catalytically active LPL, while secretion of the enzyme was effectively blocked. LPL retained intracellularly by brefeldin A treatment possessed oligosaccharide chains that were processed to the complex form by the Golgi enzymes redistributed into the ER. At 16 degrees C, a condition disrupting protein transport to the cis-Golgi, the retained enzyme again remained catalytically active although the oligosaccharides remained in the high mannose form. Lastly, attachment of the specific ER retention signal KDEL (Lys-Asp-Glu-Leu) to the carboxyl terminus of LPL also resulted in intracellularly retained enzyme that was fully active. The importance of oligosaccharide processing for attainment of LPL catalytic activity in vitro was also determined. LPL was active and secreted when trimming of the mannose residues was inhibited by deoxymannojirimycin and when addition of complex sugars was blocked using Chinese hamster ovary mutants (lec1 and lec2), indicating that these processing events are not necessary for the expression of a functional enzyme. However, blocking glucose removal by glucosidase inhibitors (castanospermine and N-methyl-deoxynojirimycin) resulted in a significant reduction in LPL specific activity and secretion. Thus, glucose trimming of LPL oligosaccharides is essential for enzyme activation; however, further oligosaccharide processing or translocation of the enzyme to the cis-Golgi is not required for full expression of lipolytic activity in vitro.
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PMID:Maturation of lipoprotein lipase. Expression of full catalytic activity requires glucose trimming but not translocation to the cis-Golgi compartment. 155 30

The present studies were designed to verify whether preventing the rise in serum levels of nonesterified fatty acids (NEFA) by adrenergic blockade would interfere with the decrease in tissue lipoprotein lipase (LPL) activity caused by acute exercise in rats. Ninety minutes before being killed, male rats were injected intraperitoneally with either saline, the beta-adrenergic blocker propranolol (25 mg/kg body weight), or the alpha 2-adrenergic blocker yohimbine (3 mg/kg body weight). Half of each group was killed at rest and the other half immediately after a 1-h run on a treadmill. LPL was determined in white adipose tissue (WAT), heart, and red vastus lateralis muscle (VLM). Exercise enhanced serum levels of NEFA 50% over resting values in saline-injected rats. The latter increase was totally abolished in animals having received propranolol or yohimbine. The activity of LPL in WAT, heart, and red VLM was approximately 35% lower in exercised rats than in resting animals. Serum triacylglycerols were also reduced by the run. Neither propranolol nor yohimbine interfered with any of these reductions. Exercise did not change serum glucose levels in saline-injected rats but decreased it in those injected with propranolol or yohimbine. Serum insulin was unchanged by exercise and by the antagonists. These findings suggest that the beta- and alpha 2-adrenergic pathways, as well as the exercise-induced rise in serum levels of NEFA, are not responsible for the early reducing effect of a 1-h run on tissue LPL activity in untrained rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum free fatty acids are not involved in acute exercise-induced reduction of LPL in rat tissues. 156 24

Streptozotocin-induced diabetes reduced cellular lipoprotein lipase (LPL) activity in cardiac myocytes from rat hearts and decreased the heparin-induced release of LPL into the medium. This effect of diabetes was rapidly reversed by in vivo treatment with insulin (5 U iv for 1 h); administration of insulin in vivo to control rats also increased heparin-releasable LPL activity. In contrast, in vitro addition of insulin to control and diabetic myocytes did not alter either cellular or heparin-releasable LPL activities. Insulin stimulated glucose oxidation and protein synthesis in control and diabetic myocytes. Decavanadate (0.05-1 mM) or vanadyl ion (0.5 mM) enhanced the release of LPL into the medium. Heparin- and decavanadate-induced release of LPL was not additive, and heparin pretreatment reduced the subsequent release of LPL by decavanadate. Decavanadate displaced LPL bound to heparin-Sepharose and increased LPL release into the perfusate of hearts. Therefore, decavanadate can mimic heparin in its effect on LPL. The absence of a direct in vitro effect of insulin on LPL in cardiac myocytes suggests that insulin may require some other in vivo factor or that diabetes-induced changes in LPL activity are secondary to some other metabolic factor.
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PMID:Lipoprotein lipase release from cardiac myocytes is increased by decavanadate but not insulin. 159 Mar 76

Short-term studies have suggested that analogs of prostaglandin E may have favorable effects on the carbohydrate and lipid metabolism in patients with type II diabetes mellitus. The present study was undertaken to investigate the long-term effects of a prostaglandin E1 analog on the regulation of glycemic control and plasma lipids. Twenty patients with type II diabetes received enisoprost, 300 mcg/day, for three months. Fasting serum glucose, glycosylated hemoglobin, insulin and C-peptide levels as well as triglyceride, total cholesterol, high density lipoprotein cholesterol and its subfractions, apolipoproteins B and AI and post-heparin lipoprotein lipase and hepatic triglyceride lipase activities were determined. During the first month, enisoprost treatment caused significant decreases in plasma glucose (baseline = 8.72 +/- 0.39 mmol/L, 4 week = 7.78 +/- 0.5 mmol/L, change = -0.94 +/- 0.28 mmol/L, p less than 0.01) and total cholesterol (baseline = 5.30 +/- 0.23 mmol/L, 4 week = 5.01 +/- 0.26 mmol/L, change = -0.28 +/- 0.06 mmol/L, p less than 0.05). The decrease in cholesterol level was due to a reduction in high density lipoprotein, specifically in high density lipoprotein2 fraction (baseline = 1.29 +/- 0.1 mmol/L, 4 week = 1.12 +/- 0.08 mmol/L, change = -0.018 +/- 0.04 mmol/L, p less than 0.05 for the former and baseline = 0.40 +/- 0.06 mmol/L, 4 week = 0.27 +/- 0.03 mmol/L, change = -0.12 +/- 0.03 mmol/L, p less than 0.05 for the latter): All of these values returned to the pretreatment levels despite continuation of enisoprost.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the prostaglandin E1 analog enisoprost on glucose and lipid metabolism in patients with type II diabetes mellitus. 160 93


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