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)

Clusterin (gene symbol: CLI) is a post-translationally nicked, two-chain plasma and tissue glycoprotein of 80 kDa. It forms high-density lipoprotein complexes with apolipoprotein A-I in plasma, functions as an inhibitor of the cytolytic reaction of the terminal complement proteins C5 to C9, and is secreted by Sertoli cells in large amounts into the seminal fluid. By isolating and characterizing three partially overlapping cosmid clones, we have established the complete physical map of the clusterin gene which spans about 20 kb. The subchromosomal position of the clusterin gene (CLI) and the order of CLI and the lipoprotein lipase (LPL) gene were determined by fluorescence in situ hybridization. We show that CLI, previously assigned to chromosome 8, is located on 8p21 proximal to the LPL locus. Based on this localization we consider clusterin as a novel candidate gene determining susceptibility to atherosclerosis.
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PMID:Human clusterin (CLI) maps to 8p21 in proximity to the lipoprotein lipase (LPL) gene. 831 91

We characterized the preweaning differences in cholesterol metabolism between breast-fed and formula-fed baboons and determined if formulas with low and high polyunsaturated:saturated fatty acid (P:S) ratios simulated the effects of breast feeding. At birth, 45 infant baboons from three sires and 44 dams were assigned to breast-fed, low P:S formula or high P:S formula diet groups until weaning at 14 wk. From 4 to 14 wk breast-fed infants had higher serum cholesterol because of much higher HDL1- and HDL2-cholesterol concentrations but had lower HDL3-cholesterol than both formula-fed groups. LDL-cholesterol was higher in infants fed the low P:S fomula. Breast-fed infants had higher serum apolipoprotein E than the formula-fed groups, but diet did not affect apolipoprotein A-I or B concentrations. Breast-fed infants had higher hepatic acyl CoA cholesterol acyltransferase activity and lower plasma lecithin cholesterol acyltransferase activity. These enzyme activities were not different between infants fed low or high P:S formulas. Post-heparinized plasma lipoprotein lipase activity was greater in breast-fed infants than in those fed formula. These findings demonstrate that the P:S ratio of formulas has little effect on cholesterol metabolism during the preweaning period and suggest that factors other than fat composition account for the metabolic differences between breast feeding and commercial infant formula.
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PMID:Infant diet affects serum lipoprotein concentrations and cholesterol esterifying enzymes in baboons. 842 64

Glycogen storage disease type I (GSD-I) is frequently complicated by severe hyperlipoproteinemia and the increased potential risk of premature atherosclerosis. The effects of fish-oil supplementation [MaxEPA, 10 g.(1.73 m2)-1 for 3 mo] were investigated prospectively in seven hyperlipoproteinemic patients with GSD-I. Hypertriglyceridemia and hypercholesterolemia improved after 3 mo of fish-oil treatment, decreasing 49% (P < 0.005) and 23%, respectively. This was accompanied by a reduction in both low-density-lipoprotein (LDL) cholesterol (25%, P < 0.03) and apolipoprotein B (40%) and by increased high-density-lipoprotein increased (HDL) cholesterol (30%, P < 0.002) and apolipoprotein A-I (31%, P < 0.05). Low pretreatment ratios of HDL to total cholesterol and HDL to LDL, indicators of elevated atherosclerosis risk, increased significantly (P < 0.05). Plasma lipoprotein profile as well as lipoprotein composition [triglyceride (TG) enrichment and cholesteryl depletion] improved. Reduced TG concentrations were due to enhanced fat catabolism, as evidenced by the significantly increased hepatic and extrahepatic lipoprotein lipase activity (P < 0.05). Withdrawal of fish oil for 3 mo was associated with a return to pretreatment abnormalities in plasma lipids and lipoproteins. Fish-oil supplementation thus improves the hyperlipoproteinemia in GSD-I and may significantly reduce the risk of premature atherosclerotic cardiovascular disease.
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PMID:Beneficial effects of fish-oil supplements on lipids, lipoproteins, and lipoprotein lipase in patients with glycogen storage disease type I. 850 63

A crossover study was conducted to examine the effects on plasma lipoprotein concentrations of substituting lean white fish (LWF) for beef, port, veal, eggs, and milk products (BPVEM) within prudent isoenergetic diets. Fourteen premenopausal women received 8784 kJ--20% as protein, 50% as carbohydrates, and 30% as lipids [ratio of polyunsaturated to monounsaturated to saturated fatty acids (P:M:S) of 1:1:1 compared with 0.4:1:1 in preexperimental diet]--and 260 mg cholesterol/d. After 4 wk, the BPVEM diet significantly reduced concentrations of plasma cholesterol, low-density-lipoprotein (LDL) cholesterol, high-density-lipoprotein (HDL) cholesterol, apolipoprotein B, HDL-apolipoprotein A-I, and LDL-apolipoprotein B (P<0.05) as well as plasma postheparin hepatic triacylglycerol lipase activity compared with the preexperimental diet. These effects are probably attributable to elevation of the P:M:S. These responses were not observed with the LWF diet, suggesting that fish protein in LWF maintains unchanged plasma cholesterol concentrations despite a high P:M:S. The LWF diet, compared with the preexperimental diet, reduced very-low-density-lipoprotein triacylglycerol (P<0.05) and also the ratio of LDL cholesterol to apolipoprotein B (P<0.05), revealing the presence of denser LDL particles. Compared with the BPVEM diet, the LWF diet induced lower concentrations of very-low-density-lipoprotein triacylglycerols (P<0.05) and higher concentrations of LDL triacylglycerol and LDL apolipoprotein B (P<0.05), which were not associated with any increase in lipoprotein lipase activity. These results suggest that LWF as a substitute for BPVEM in isoenergetic diets with an elevated P:S produces minimal improvement in the lipoprotein profile in premenopausal women.
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PMID:Plasma lipoprotein profile and lipolytic activities in response to the substitution of lean white fish for other animal protein sources in premenopausal women. 860 86

The hypertriglyceridemia commonly observed in uremia has been attributed to an abnormally high inhibitor activity in plasma for lipoprotein lipase (LPL) and hepatic lipase (HL), both of which have a key role in lipoprotein metabolism. The purpose of this investigation was to establish a relationship between plasma lipase inhibitor activity and hypertriglyceridemia, identify the main plasma lipase inhibitor, and determine the basis for the greater inhibitor activity in uremia. In a mixed population of normal (N = 8) and uremic subjects (N = 12), log-transformed plasma triglycerides correlated with both inhibitor activity and uremic status. However, inhibitor activity was the only retained predictor variable for triglycerides in a multiple linear regression model (r = 0.91; P < 0.0001). An inhibitor isolated from normal plasma was identified as a particle containing apolipoprotein A-I (apo A-I) and 3% phospholipid. This particle, which has pre-beta electrophoretic mobility and a Stokes' radius of 54 A, therefore corresponds to a form of the previously described pre-beta-HDL (free apo A-I) in the non-lipoprotein fraction of plasma. Comparison of normal and uremic plasma indicated that the greater lipase inhibitor activity in the latter could be attributed to an increased concentration of apo A-I in the non-lipoprotein fraction of plasma (pre-beta-HDL), as well as to increased inhibition by the uremic lipoproteins. The increased plasma lipase inhibitor activity may be important in the pathogenesis of hypertriglyceridemia in chronic renal failure.
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PMID:Increased lipase inhibition in uremia: identification of pre-beta-HDL as a major inhibitor in normal and uremic plasma. 873 Nov 1

Most known mutations underlying human lipoprotein abnormalities affect the protein coding sequence of the gene involved. Mutations in the regulatory regions-promoters, enhancers, binding sites for transcription factors and other elements-may markedly alter the transcription efficiency of lipid-regulatory genes, and may thus cause an inherited defect of lipoprotein metabolism. Reported examples include mutations of the promoters of the human LDL and lipoprotein lipase genes. Common variation of the DNA sequence in the promoter region, such as that occurring in the human apolipoprotein A-I and plasminogen activator inhibitor(-1) genes, may account for subtle differences in serum lipid levels and risk of atherosclerotic vascular disease in the general population.
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PMID:Regulatory mutations in human lipoprotein disorders and atherosclerosis. 874 97

Apolipoprotein A-I plays an essential structural and functional role in HDL metabolism and apolipoprotein A-II has important effects on HDL metabolism and function. Kinetic studies in humans have established that variation in plasma HDL-cholesterol and apolipoprotein A-I concentrations is primarily determined by variation in the rate of apolipoprotein A-I catabolism. In contrast, plasma apolipoprotein A-II levels are primarily determined by the rate of apolipoprotein A-II production. Genetic factors play an important role in modulating the plasma levels of HDL-cholesterol and apolipoproteins A-I and A-II. Studies in humans have established that mutations in genes encoding enzymes that esterify cholesterol (lecithin : cholesterol acyltransferase), transfer cholesterol (cholesteryl ester transfer protein) and hydrolyze lipids (hepatic lipase, lipoprotein lipase) regulate HDL-cholesterol and apolipoprotein A-I levels by modifying the lipid content (and therefore the size) of HDL particles. Recent studies in transgenic and knockout animals have confirmed the key role of HDL lipid-modifying proteins in HDL, apolipoprotein A-I and apolipoprotein A-II metabolism and have expanded our understanding of the role of lipid modification in determining plasma concentrations of HDL-cholesterol and apolipoprotein A-I, as well as the potential functional roles of apolipoprotein A-II.
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PMID:Unravelling high density lipoprotein-apolipoprotein metabolism in human mutants and animal models. 881 7

New approaches to the study of the genetics of premature coronary heart disease (CHD) have been made possible by the introduction of DNA probes for the apolipoproteins, the receptors and enzymes involved in lipid transport. Initially these were used to identify restriction fragment length polymorphisms for use as genetic markers to locate genes involved in the pathogenesis of atherosclerosis. More recent developments have allowed direct analysis of etiological mutations by such methods as single stranded conformational polymorphism (SSCP) analysis and denaturing gradient gel electrophoresis (DGGE). Loci that have been incriminated by such techniques include the apolipoprotein A-I--C-III--A-IV gene cluster, the apo B gene and the lipoprotein lipase locus. It is to be anticipated that these and other techniques will eventually identify all the major determinants involved in disorders of lipid transport and the development of premature atherosclerosis.
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PMID:Genetic determinants of atherosclerosis-related dyslipidemias and their clinical implications. 911 62

Previous studies in growth hormone (GH)-deficient or acromegalic patients yielded contradictory results on the effect of GH on lipoprotein metabolism. In a cross-sectional study, we analyzed the relationships between unstimulated GH, insulin-like growth factor 1 (IGF1), insulin, and lipoprotein metabolism in 44 non-obese young women. On univariate analysis, basal serum levels of GH correlated positively with triglycerides, high-density lipoprotein (HDL) cholesterol, apolipoprotein A-I (apoA-I) and apoA-II and negatively with lipoprotein lipase (LPL) activity. These associations remained significant on multivariate analyses that, in addition to GH, took into account the effects of insulin or C-peptide, as well as the effects of total, protein-bound, or free IGF1. In most cases, the relationships of these lipid parameters with insulin/C-peptide and IGF1 and its free or protein-bound subfractions were opposite of those with GH and not significant. Thus, GH appears to regulate the metabolism of HDL and triglycerides independently of IGF1 and insulin.
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PMID:Basal growth hormone levels in women are positively correlated with high-density lipoprotein cholesterol and apolipoprotein A-I independently of insulin-like growth factor 1 or insulin. 950 May 74

To study the role of low levels of high density lipoprotein (HDL) and apolipoprotein (apo) A-I in atherosclerosis risk, human apoB transgenic mice (HuBTg) were crossed with apoA-I-deficient (apoA-I-/-) mice. After a high fat challenge, total cholesterol levels increased drastically due to an increase in the non-HDL cholesterol as confirmed by FPLC analysis. In addition, total cholesterol levels in A-I-/- HuBTg mice were lower than the control HuBTg mice, due mainly to decreased HDL-C in A-I-/- HuBTg mice. Analysis of atherosclerosis in the proximal aorta in mice fed a high-fat Western-type diet for 27 weeks revealed a 200% greater lesion area in female apoA-I-/- HuBTg mice (49740+/-9751 microm2) compared to control HuBTg mice (23320+/-4981 microm2, P = 0.03). Lesion size (12380+/-3281 microm2) in male A-I-/- HuBTg mice was also about 200% greater than that in the control HuBTg mice (5849+/-1543 microm2), although not statistically significant. Very few and small lesions were observed in both apoA-I-/- HuBTg and control HuBTg animals fed a chow diet. Therefore, the adverse effect of low HDL on atherosclerosis in mice was only evident when LDL-cholesterol was markedly elevated by high-fat challenge. Male apoA-I-/- HuBTg mice exhibited hypertriglyceridemia when challenged with a high-fat diet. This correlated with both a reduction in lipoprotein lipase activity and a decrease in lipoprotein lipase activation by HDL. In summary, low high density lipoprotein levels due to apolipoprotein A-I deficiency exacerbated the development of atherosclerotic lesions in mice with elevated atherogenic lipoproteins. This mouse model mimics human conditions associated with low HDL levels and provides additional evidence for the anti-atherogenic role of apoA-I.
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PMID:ApoA-I deficiency causes both hypertriglyceridemia and increased atherosclerosis in human apoB transgenic mice. 950 92


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