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:3.1.1.34 (lipoprotein lipase)
7,025 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The carrier frequency of Asn291Ser polymorphism of the lipoprotein lipase (LPL) gene is 4;-6% in the Western population. Heterozygotes are prone to fasting hypertriglyceridemia and low high density lipoprotein (HDL) cholesterol concentrations especially when secondary factors are superimposed on the genetic defect. We studied the LPL Asn291Ser gene variant as a modulator of postprandial lipemia in heterozygote carriers. Ten normolipidemic carriers were compared to ten control subjects, who were selected to have similar age, sex, BMI, and apolipoprotein (apo)E-phenotype. The subjects were given a lipid-rich mixed meal and their insulin sensitivity was determined by euglycemic hyperinsulinemic clamp technique. The two groups had comparable fasting triglycerides and glucose utilization rate during insulin infusion, but fasting HDL cholesterol was lower in carriers (1.25 +/- 0.05 mmol/L) than in the control subjects (1. 53 +/- 0.06 mmol/L, P = 0.005). In the postprandial state the most pronounced differences were found in the very low density lipoprotein 1 (VLDL1) fraction, where the carriers displayed higher responses of apoB-48 area under the curve (AUC), apoB-100 AUC, triglyceride AUC, and retinyl ester AUC than the control subjects. The most marked differences in apoB-48 and apoB-100 concentrations were observed late in the postprandial period (9 and 12 h), demonstrating delayed clearance of triglyceride-rich particles of both hepatic and intestinal origin. Postprandially, the carriers exhibited enrichment of triglycerides in HDL fraction. Thus, in normolipidemic carriers the LPL Asn291Ser gene variant delays postprandial triglyceride, apoB-48, apoB-100, and retinyl ester metabolism in VLDL1 fraction and alters postprandial HDL composition compared to matched non-carriers.
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PMID:Delayed clearance of postprandial large TG-rich particles in normolipidemic carriers of LPL Asn291Ser gene variant. 1048 13

Triglyceride-rich lipoprotein (TRL) remnants are formed in the circulation when apolipoprotein (apo) B-48-containing chylomicrons of intestinal origin or apoB-100-containing VLDL of hepatic origin are converted by lipoprotein lipase, and to a lesser extent by hepatic lipase, into smaller and more dense particles. Compared with their nascent precursors, TRL remnants are depleted of triglyceride, phospholipid, and C apolipoproteins and are enriched in cholesteryl esters and apoE. They can thus be identified, separated, and/or quantified in plasma according to their density, charge, size, specific lipid components, apolipoprotein composition, and/or apolipoprotein immunospecificity. Each of these approaches has contributed to our current understanding of the compositional characteristics of TRL remnants and their potential to promote atherosclerosis. An ongoing search is nevertheless under way for more accurate and clinically applicable remnant lipoprotein assays that will be able to better define coronary artery disease risk in patients with hypertriglyceridemia.
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PMID:Detection, quantification, and characterization of potentially atherogenic triglyceride-rich remnant lipoproteins. 1052 78

Familial hypercholesterolemia is characterized by a high plasma LDL-cholesterol level. The low-density particles are the end-product of the triglyceride-rich particles, i.e. VLDL, synthetized by the liver. These triglyceride-rich particles are subsequently transformed into intermediate density lipoprotein by the lipoprotein lipase and LDL after further triglyceride hydrolysis by the hepatic lipase. The LDL particles are taken up in all cells by the mean of the LDL receptor. A large body of evidence (including experimental, clinical, epidemiological data as well as the results of large trial with lipid lowering drugs) has accumulated to establish that these particles are one of the major causative factor of atherosclerosis and its complications. Two different mechanisms may be at work in the familial hypercholesterolemia: a mutation in the LDL receptor or a single mutation in the apolipoprotein B100. Specific therapeutic intervention should be undertaken to decrease the risk to develop cardiovascular disease, mainly coronary heart disease. The therapeutic intervention includes both a diet low in saturated fatty acids and cholesterol and statins which are now the first line therapy. Fibrates are proposed to those who do not tolerate statins and LDL-apheresis is associated to statin in the rare homozygous familial hypercholesterolemia.
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PMID:[Familial hypercholesterolemia]. 1068 42

A mouse model of insulin resistance and its associated dyslipidemia was generated by crossing mice expressing human apolipoprotein B (apoB) with mice lacking only brown adipose tissue (BATless). On a high fat diet, male apoB/BATless mice became obese, hypercholesterolemic, hypertriglyceridemic, and hyperinsulinemic compared with control apoB mice. Fast performance liquid chromatography revealed increased triglyceride concentrations in intermediate density lipoprotein/low density lipoprotein (LDL) and reduced high density lipoprotein cholesterol concentrations. Inhibition of lipolysis by the drug, tetrahydrolipostatin, demonstrated that very low density lipoprotein-sized particles were initially secreted. Metabolic studies employing Triton WR-1339 and either [(3)H]glycerol or [(3)H]palmitate showed that the hypertriglyceridemia in apoB/BATless mice was due to the increased synthesis and secretion of triglyceride. Furthermore, lipoprotein lipase and hepatic lipase activities were not defective. ApoB was also secreted at increased rates in the apoB/BATless mice. Similar levels of apoB mRNA in apoB and apoB/BATless mice indicated that apoB secretion was regulated post-transcriptionally. LDL receptor mRNA was increased in the apoB/BATless mice, indicating that the observed increase in apoB-lipoprotein secretion was not due to their decreased reuptake. Finally, mRNA levels of the large subunit of microsomal triglyceride transfer protein, a required component for very low density protein assembly, were not different between apoB and apoB/BATless mice. This rodent model should prove useful in exploring mechanisms underlying the regulation of apoB secretion in the context of insulin resistance.
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PMID:Post-transcriptional stimulation of the assembly and secretion of triglyceride-rich apolipoprotein B lipoproteins in a mouse with selective deficiency of brown adipose tissue, obesity, and insulin resistance. 1159 38

The effects of long-term chronic growth hormone (GH) excess on lipid and lipoprotein metabolism were investigated in 8-mo-old bovine GH (bGH)-transgenic mice. Total body weight, serum cholesterol, insulin-like growth factor-I, and insulin levels were higher, whereas serum levels of glucose, free fatty acids, and triglycerides were lower in transgenic mice. Very low-density lipoprotein (VLDL) cholesterol levels were lower, and low-density lipoprotein (LDL) cholesterol levels were higher, in transgenic mice irrespective of gender, whereas only transgenic male mice had higher high-density lipoprotein cholesterol levels. Total serum apolipoprotein B (apoB) levels were not affected, but the amount of apoB in the LDL fraction was higher in transgenic mice. Hepatic LDL receptor expression was unchanged, whereas apoB mRNA editing and hepatic triglyceride secretion rate were reduced in bGH-transgenic male mice. Both lipoprotein lipase activity in adipose and heart tissue and beta-adrenergic-stimulated lipolysis were increased in transgenic male mice. The relative weight of adipose tissue was lower in transgenic mice, whereas hepatic triglyceride content was unchanged. Fat feeding of the mice equalized serum triglycerides and free fatty acids in bGH-transgenic and control mice. In summary, long-term GH excess is associated with marked alterations in lipid and lipoprotein metabolism, indicating decreased production and increased degradation of VLDL and preferential flux of fatty acids to muscle tissues.
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PMID:Long-term growth hormone excess induces marked alterations in lipoprotein metabolism in mice. 1170 38

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.
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PMID:Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients. 1176 56

Apolipoprotein E (apoE) is essential for the clearance of plasma chylomicron and VLDL remnants. The human APOE locus is polymorphic and 5-10% of APOE*2 homozygotes exhibit type-III hyperlipoproteinemia (THL), while the remaining homozygotes have less than normal plasma cholesterol. In contrast, mice expressing APOE*2 in place of the mouse Apoe (Apoe(2/2) mice) are markedly hyperlipoproteinemic, suggesting a species difference in lipid metabolism (e.g., editing of apolipoprotein B) enhances THL development. Since apoB-100 has an LDLR binding site absent in apoB-48, we hypothesized that the Apoe(2/2) THL phenotype would improve if all Apoe(2/2) VLDL contained apoB-100. To test this, we crossed Apoe(2/2) mice with mice lacking the editing enzyme for apoB (Apobec(-/-)). Consistent with an increase in remnant clearance, Apoe(2/2). Apobec(-/-) mice have a significant reduction in IDL/LDL cholesterol (IDL/LDL-C) compared with Apoe(2/2) mice. However, Apoe(2/2).Apobec(-/-) mice have twice as much VLDL triglyceride as Apoe(2/2) mice. In vitro tests show the apoB-100-containing VLDL are poorer substrates for lipoprotein lipase than apoB-48-containing VLDL. Thus, despite a lowering in IDL/LDL-C, substituting apoB-48 lipoproteins with apoB-100 lipoproteins did not improve the THL phenotype in the Apoe(2/2).Apobec(-/-) mice, because apoB-48 and apoB-100 differentially influence the catabolism of lipoproteins.
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PMID:ApoB-48 and apoB-100 differentially influence the expression of type-III hyperlipoproteinemia in APOE*2 mice. 1223 84

Omega-3 fatty acids (FAs) reduce postprandial triacylglycerol (TG) concentrations. This study was undertaken to determine whether this effect was due to reduced production or increased clearance of chylomicrons. Healthy subjects (n = 33) began with a 4-week, olive oil placebo (4 g/d) run-in period. After a 4-week wash-out period, subjects were randomized to supplementation with 4 g/d of ethyl esters of either safflower oil (SAF), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) for 4 weeks. Results for EPA and DHA were similar, and therefore the data were combined into one omega-3 FA group. Omega-3 FA supplementation reduced the postprandial TG and apolipoprotein B (apo B)-48 and apoB-100 concentrations by 16% (P = 0.08), 28% (P < 0.001), and 24% (P < 0.01), respectively. Chylomicron TG half-lives in the fed state were reduced after omega-3 FA treatment (6.0 +/- 0.5 vs. 5.1 +/- 0.4 min; P < 0.05), but not after SAF (6.9 +/- 0.7 vs. 7.1 +/- 0.7 min). Omega-3 FA supplementation decreased chylomicron particle sizes (mean diameter; 293 +/- 44 vs. 175 +/- 25 nm; P < 0.01) and increased preheparin lipoprotein lipase (LPL; 0.6 +/- 0.1 vs. 0.9 +/- 0.1 micromol/h/ml; P < 0.05) activity during the fed state, but had no effect on postheparin LPL or hepatic lipase activities. The results suggest that omega-3 FA supplementation accelerates chylomicron TG clearance by increasing LPL activity, and that EPA and DHA are equally effective.
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PMID:Omega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance. 1256 65

It is generally believed that vitamin E is absorbed along with chylomicrons. However, we previously reported that human colon carcinoma Caco-2 cells use dual pathways, apolipoprotein B (apoB)-lipoproteins and HDLs, to transport vitamin E. Here, we used primary enterocytes and rodents to identify in vivo vitamin E absorption pathways. Uptake of [(3)H]alpha-tocopherol by primary rat and mouse enterocytes increased with time and reached a maximum at 1 h. In the absence of exogenous lipid supply, these cells secreted vitamin E with HDL. Lipids induced the secretion of vitamin E with intermediate density lipoproteins, and enterocytes supplemented with lipids and oleic acid secreted vitamin E with chylomicrons. The secretion of vitamin E with HDL was not affected by lipid supply but was enhanced when incubated with HDL. Microsomal triglyceride transfer protein inhibition reduced vitamin E secretion with chylomicrons without affecting its secretion with HDL. Enterocytes from Mttp-deficient mice also secreted less vitamin E with chylomicrons. In vivo absorption of [(3)H]alpha-tocopherol by mice after poloxamer 407 injection to inhibit lipoprotein lipase revealed that vitamin E was associated with triglyceride-rich lipoproteins and small HDLs containing apoB-48 and apoA-I. These studies indicate that enterocytes use two pathways for vitamin E absorption. Absorption with chylomicrons is the major pathway of vitamin E absorption. The HDL pathway may be important when chylomicron assembly is defective and can be exploited to deliver vitamin E without increasing fat consumption.
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PMID:Mechanisms involved in vitamin E transport by primary enterocytes and in vivo absorption. 1758 42

Hypertriacylglycerolaemia is an important risk factor for cardiovascular disease. In men, we have shown that the effects of evening exercise on basal VLDL (very-low-density lipoprotein) metabolism are dose-dependent: a single prolonged bout of aerobic exercise [2 h at 60% of VO(2 peak) (peak oxygen consumption)] reduces fasting plasma TAG [triacylglycerol (triglyceride)] concentrations, via enhanced clearance of VLDL-TAG from the circulation, whereas the same exercise performed for 1 h has no effect on VLDL-TAG metabolism and concentration. We hypothesized that women are more sensitive to the TAG-lowering effect of exercise because they reportedly use more intramuscular TAG as an energy source during exercise, and depletion of muscle TAG stores has been linked to reciprocal changes in skeletal muscle LPL (lipoprotein lipase) activity. To test our hypothesis, we measured basal VLDL-TAG and VLDL-apoB-100 (apolipoprotein B-100), and plasma NEFA [non-esterified fatty acid ('free fatty acid')] kinetics, by using stable isotope-labelled tracer techniques, on the morning after a single session of evening exercise of moderate duration and intensity (1 h at 60% of VO(2 peak)) in eight sedentary pre-menopausal women (age, 28+/-3 years; body mass index, 27+/-2 kg/m(2); body fat, 34+/-3%; values are means+/-S.E.M.). Compared with an equivalent period of evening rest, exercise had no effect on post-absorptive NEFA concentrations and the rate of appearance in plasma, VLDL-TAG and VLDL-apoB-100 concentrations, hepatic VLDL-TAG and VLDL-apoB-100 secretion and plasma clearance rates (all P>0.05). We conclude that, in women, as in men, a single session of exercise of moderate intensity and duration is not sufficient to bring about the alterations in VLDL metabolism that have been linked to post-exercise hypotriacylglycerolaemia.
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PMID:Basal adipose tissue and hepatic lipid kinetics are not affected by a single exercise bout of moderate duration and intensity in sedentary women. 1875 66


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