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

The liver plays a central role in lipoprotein metabolism. In particular, very-low density lipoprotein (VLDL) is assembled in the hepatocytes and secreted into the blood circulation. The VLDL is then catabolized to low-density lipoprotein by lipoprotein lipase and hepatic triglyceride lipase. Obese subjects, especially those with visceral fat accumulation, are frequently associated with hyperlipidemia, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. The mechanism of hyperlipidemia in visceral fat obesity has not yet been elucidated. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity with visceral fat accumulation, hyperlipidemia, and late-onset insulin resistance. To elucidate the mechanism of hyperlipidemia observed in OLETF rats, we focused on the production of VLDL by the liver and investigated hepatic messenger RNA (mRNA) levels of microsomal triglyceride transfer protein (MTP), acyl-coenzyme A synthetase (ACS), and apolipoprotein B (apo B), which play important roles in VLDL synthesis and secretion. In 6-week-old OLETF rats, in which insulin resistance had not been manifested, visceral fat weight was already higher and portal free fatty acid (FFA) and VLDL-triglyceride levels were elevated compared with the control rats. Hepatic ACS activity and mRNA levels, and MTP mRNA levels were also increased in OLETF rats, whereas apo B mRNA levels were similar; these results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation before developing insulin resistance may be involved in the pathogenesis of hyperlipidemia in obese animal models with NIDDM.
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PMID:Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation. 946 57

The association of genetic markers at the apolipoprotein B gene (APOB) (XbaI, MspI, and EcoRI polymorphisms) and the lipoprotein lipase gene (LPL) (PvuII polymorphism) with coronary artery disease (CAD) and with variation in plasma lipid levels (total cholesterol, high-density lipoprotein cholesterol, and total triglycerides) was studied in 94 male patients with CAD diagnosed by angiography and in 122 unrelated men of Russian descent free of clinical signs of CAD. The frequent allele (M+) of the APOB MspI RFLP was seen more frequently in CAD patients than in control subjects (0.963 vs. 0.898, p < 0.025). No significant differences in allele frequencies were observed for the APOB XbaI and EcoRI polymorphisms or for the LPL PvuII polymorphism. In patients, carriers of the rare allele (E-) of the EcoRI RFLP had higher mean triglyceride levels than homozygotes for E+ (p < 0.05). No significant differences in lipid variables were determined for the other three polymorphisms studied. Analysis of intragenotype variances and the multivariate measure of mean values of lipid concentrations showed that genetic variability within the APOB locus may contribute to a certain extent to the level and variability of serum lipid levels in this Russian population.
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PMID:Genetic markers in coronary artery disease in a Russian population. 948 34

Coronary heart disease (CHD) has been considered as a multifactorial disorder with the involvement of both environmental and genetic factors. The advent of tools to investigate individual variability of DNA has allowed us to perform the association studies of candidate genes. However, an association between genetic trait and phenotypic variations is not easy to demonstrate and several reported association between genetic markers and risk factors or overt CHD have gone unconfirmed. It should not be assumed that for a given genetic trait, the impact on risk will be similar in all populations. In particular, most studies of the molecular bases of CHD have involved Caucasian subjects, so much more work with the Korean population is needed before genetic testing for susceptibility to CHD can be offered to Koreans as a clinical service. In this review, we discuss two aspects of the molecular bases of CHD: i) Molecular bases of the candidate gene related to lipoprotein metabolism including apolipoprotein AI-CIII-AIV gene duster, apolipoprotein B, apolipoprotein E-CI-CII gene cluster, apolipoprotein(a), LDL receptors, lipoprotein lipase, cholesteryl ester transfer protein, and apo B editing protein; ii) Molecular bases of the candidate gene related to thrombotic and other factors including fibrinogen, factor VII, plasminogen activator inhibitor 1, homocysteine, stromelysin, paraoxonase, and angiotensin converting enzyme. Studies involving the Korean population, especially those performed by our teams, are also summarized.
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PMID:Molecular bases of coronary heart disease in Koreans. 953 12

Low concentrations of high-density lipoprotein cholesterol (HDL-C) are a recognized risk factor for atherosclerotic cardiovascular disease. Exercise is often recommended to increase HDL-C, but the effect of exercise training on HDL levels and metabolism in subjects with low HDL concentrations is not well defined. The present study compared the HDL response to 12 months of supervised endurance exercise training without weight loss in 17 men aged 26 49 years with initially low ( < 40 mg/dl, N=7) or normal ( > 44 mg/dl, N=10) HDL-C levels. HDL-C levels and HDL apolipoprotein metabolism were assessed while the subjects consumed controlled diets before and after the year of training. Increases in total (5.1+/-2.8 versus 1.9+/-4.2 mg/dl, P=0.08) and HDL2 (3.8+/-2.9 versus 0.4+/-1.1 mg/dl, P=0.01) cholesterol were greater in men with normal initial HDL-C levels. Catabolic rates for HDL apolipoproteins decreased 7-14% and biological half-lives increased 10-15% after exercise training in subjects with normal HDL, but were unchanged in the low HDL-C group. HDL apolipoprotein synthetic rates were not consistently affected by exercise training in either group. Postheparin lipoprotein lipase activity increased 27%, the clearance rate of intravenous triglycerides increased 14%, and apolipoprotein B levels decreased 16% with training in subjects with normal HDL-C but were unchanged in the low HDL-C group. We conclude that the ability to increase HDL-C levels through endurance exercise training is limited in subjects with low initial HDL-C, possibly because exercise training in such subjects fails to alter triglyceride metabolism.
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PMID:Exercise training has little effect on HDL levels and metabolism in men with initially low HDL cholesterol. 956 55

The effect of bezafibrate on plasma lipoproteins was investigated in Japanese familial combined hyperlipidemic patients with or without an impaired glucose tolerance accompanied by a low-density lipoprotein subclass, with the major gradient gel peak at a particle diameter of less than 25.5 nm. Bezafibrate treatment at a dose of 400 mg/d for 12 weeks produced an antiatherogenic effect on lipoprotein profiles, as reflected by a decrease in plasma triglyceride levels, an increase in plasma high-density lipoprotein-cholesterol levels, induction of the large-size subclass of low-density lipoprotein, and disappearance of intermediate-density lipoproteins. The plasma total and low-density lipoprotein-cholesterol-lowering effect of bezafibrate was significant in patients without impaired glucose tolerance but was not significant in patients with impaired glucose tolerance. Bezafibrate increased lipoprotein lipase activity and decreased the activity of cholesteryl ester transfer protein, both in patients with or without impaired glucose tolerance. There was no difference in the distribution of signal peptide insertion/deletion or Xbal polymorphisms of the apolipoprotein B gene in patients with or without impaired glucose tolerance. Mechanisms other than lipoprotein lipase, cholesteryl ester transfer protein activities, and an apolipoprotein B gene polymorphism may be responsible for the resistance to lowering of plasma total and low-density lipoprotein cholesterol levels with bezafibrate treatment in familial combined hyperlipidemic patients with impaired glucose tolerance.
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PMID:Comparison of the effect of bezafibrate on improvement of atherogenic lipoproteins in Japanese familial combined hyperlipidemic patients with or without impaired glucose tolerance. 960 27

Epidemiological evidence shows that a diet high in monounsaturated fatty acids (MUFA) but low in saturated fatty acids (SFA) is associated with reduced risk of CHD. The hypocholesterolaemic effect of MUFA is known but there has been little research on the effect of test meal MUFA and SFA composition on postprandial lipid metabolism. The present study investigated the effect of meals containing different proportions of MUFA and SFA on postprandial triacylglycerol and non-esterified fatty acid (NEFA) metabolism. Thirty healthy male volunteers consumed three meals containing equal amounts of fat (40 g), but different proportions of MUFA (12, 17 and 24% energy) in random order. Postprandial plasma triacylglycerol, apolipoprotein B-48, cholesterol, HDL-cholesterol, glucose and insulin concentrations and lipoprotein lipase (EC 3.1.1.34) activity were not significantly different following the three meals which varied in their levels of SFA and MUFA. There was a significant difference in the postprandial NEFA response between meals. The incremental area under the curve of postprandial plasma NEFA concentrations was significantly (P = 0.03) lower following the high-MUFA meal. Regression analysis showed that the non-significant difference in fasting NEFA concentrations was the most important factor determining difference between meals, and that the test meal MUFA content had only a minor effect. In conclusion, varying the levels of MUFA and SFA in test meals has little or no effect on postprandial lipid metabolism.
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PMID:The effect of test meal monounsaturated fatty acid: saturated fatty acid ratio on postprandial lipid metabolism. 968 60

Hypertriglyceridemia is a heterogeneous lipid disorder often running in families. Variation in the apolipoprotein B (apo B) gene has been associated with serum triglyceride levels. Recently, a role of the amino-terminal end of apo B in binding with lipoprotein lipase (LPL) has been suggested. We screened the 5' end of the apo B gene in 76 Finnish severely hypertriglyceridemic (> 6 mmol/l) patients, using a single-strand conformation polymorphism (SSCP) screening method. We detected a previously unreported polymorphic C2316-->A change, causing a Val703-->Ile substitution. The minor 703 Ile allele frequency was 0.04 in hypercholesterolemic and normolipidemic population samples. This allele was associated with lower serum triglyceride levels in a normolipidemic population sample. Analysis of two previously reported polymorphisms also located in the amino-terminal domain of apo B (Thr71-->Ile and Val591-->Ala) revealed elevating effects on serum apo B concentrations in hypertriglyceridemic individuals. The 591 Ala allele was associated with elevated apo B (P=0.011), and individuals with both minor alleles (apo B 591 Ala + and apo B 71 Ile +) had higher apo B levels compared to subjects homozygous for both common alleles (P=0.004). Although no DNA sequence change seemed to be the cause of hypertriglyceridemia in our patients, genetic variation in the 5' end of the apo B gene may contribute to changes in serum apo B levels in hypertriglyceridemic patients.
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PMID:Genetic variation in the amino-terminal part of apolipoprotein B: studies in hyperlipidemic patients. 969 Sep 21

Postprandial lipaemic responses to two test meals were investigated in 30 Northern (15 British and 15 Irish), and 30 Southern (Greeks from Crete) healthy male Europeans. The meals were a saturated fatty acid (SFA) meal, which resembled the fatty acid composition of an average UK diet, and a monounsaturated fatty acid (MUFA) meal in which the fat consisted of olive oil. Habitual diets of the two groups differed, with higher total fat, (P < 0.03) and MUFA (P < 0.0001) and lower polyunsaturated fatty acid (PUFA) (P < 0.0001) intakes in Southern than Northern Europeans. Levels of total MUFA (P < 0.02) and oleic acid (P < 0.004) were also higher in adipose tissue of Southern in comparison to Northern Europeans. In both European groups there were no significant differences in postprandial triglyceride response between the two meal types, SFA or MUFA. However, Northern and Southern Europeans showed significant differences in their patterns of postprandial response in plasma triglycerides (P < 0.0001), apolipoprotein B-48 (P < 0.0001), NEFA (P < 0.0001), insulin (P < 0.0007), and factor VII activity (P-0.03). In the case of NEFA, areas under the response curve were higher following the SFA than the MUFA meal for both groups, (P < 0.003) and were greater in Southern than Northern Europeans (P < 0.002) and apo B-48 responses were lower (P < 0.005). Some of these differences may reflect differences in fasting levels since fasting apolipoprotein B-48 levels were lower (P < 0.01) and fasting NEFA (P < 0.02) and insulin (P < 0.005) were higher in the Southern than in the Northern Europeans. In addition, 9 h postprandial post-heparin lipoprotein lipase activity was lower in the Southern than in the Northern Europeans (P < 0.0006). This is the first report of differences in postprandial lipid, factor VII and insulin responses in Southern and Northern Europeans which may be of importance in explaining the different susceptibilities of these two populations to risk of coronary artery disease.
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PMID:Differences in postprandial lipaemic response between Northern and Southern Europeans. 969 95

Men with low-density lipoprotein receptor gene mutations causing familial hypercholesterolemia (FH) are at high risk of premature coronary artery disease (CAD). The dyslipidemic state found among patients who are heterozygous for mutations in the lipoprotein lipase (LPL) gene may also increase the risk of CAD. In the present study, the association of the heterozygous forms of low-density lipoprotein receptor gene mutations causing FH as well as of LPL gene mutations causing (P207L and G188E) or not causing (D9N and N291S) complete loss of LPL activity with angiographically assessed CAD was estimated in a cohort of 412 French Canadian men aged <60 years who consecutively underwent coronary angiography for the investigation of retrosternal pain. The frequency of FH as well as of LPL gene mutations tended to increase with the number of narrowed coronary arteries. However, CAD occurred earlier in FH patients than in partly LPL-deficient patients. Indeed, the proportion of men affected by FH was of 16.4% in those <45 years of age, and solely 4.3% among those between 56 and 60 years of age (p <0.0001). In contrast, the LPL gene defect was found in only 4.0% of men aged <45 years, whereas this prevalence reached 8.3% among those aged 56 to 60 years. In multivariate analyses, the association of LPL with CAD was not independent of age, high-density lipoprotein cholesterol concentrations, and other covariates included at baseline, and was not affected by the type of mutation in the LPL gene. In contrast, FH was associated with CAD with minimal contribution of other cardiovascular risk factors. However, the relation between FH and CAD was at least partly dependent on plasma apolipoprotein B concentrations. In the different regression models, fasting insulin and plasma high-density lipoprotein cholesterol concentrations were important covariates of CAD, whether or not patients were affected by FH or LPL deficiency. In conclusion, the association of LPL gene mutations with CAD was delayed compared with FH, appeared to be markedly exacerbated by the presence of additional risk factors, and was not affected by the type of mutation in the LPL gene.
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PMID:Relative contribution of low-density lipoprotein receptor and lipoprotein lipase gene mutations to angiographically assessed coronary artery disease among French Canadians. 970 57

We analyzed two-locus disequilibria for 16 polymorphic loci of seven susceptibility genes for coronary artery disease located in five chromosomal regions distributed across four chromosomes. Included were the genes coding for apolipoprotein B (ApoB, chromosome 2, four marker loci), lipoprotein lipase (LPL, chromosome 8, three marker loci), apolipoproteins AI, CIII AIV (ApoAI-CIII-AIV, chromosome 11, three marker loci), apolipoprotein E (ApoE, chromosome 19, two marker loci), and the low density lipoprotein receptor (LDLR, chromosome 19, four marker loci). Our sample included 540 unrelated individuals from the Rochester, Minn. population. There were no statistically significant deviations of single-locus genotypes from Hardy-Weinberg equilibrium. The strongest associations within genes were for composite diallelic disequilibria; 17/19 were significant (13 at Pr <0.001, 1 at Pr <0.01, 3 at Pr <0.05). These observations suggest marker alleles within genes have a shared evolutionary history reflected by disequilibria that have not been dissipated by recombination. Disequilibrium was not generally concordant with the physical orderings of markers. Only two significant higher-order disequilibria were observed although 12 triallelic disequilibria were at maximum possible values. We observed 19 statistically significant disequilibria (Pr <0.05; 4 composite diallelic, 13 triallelic, and 2 quadriallelic) between 101 pairs of marker loci, where each locus in a pair was from a different unlinked region. These unexpected results are most likely explained by recent historical factors, including worldwide population expansion and amalgamation with continuous admixture, that influence the genetic structure (organization of alleles and non-alleles into genotypes) of a population. We conclude that disequilibria between loci from unlinked regions may be more extensive than is commonly assumed. Our findings also suggest that it is, on average, at least 15 times more likely to not detect significant disequilibrium among unlinked loci when it is really present than to make a false positive inference. Disequilibria between functional loci within or between regions will impact estimates of genetic variance associated with particular functional mutations within a susceptibility gene region.
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PMID:Genetic structure of five susceptibility gene regions for coronary artery disease: disequilibria within and among regions. 979 92


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