Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to determine the effects of country liquor Toddy and its equivalent quantity of ethanol on lipid metabolism during gestation in rats. Female rats weighing an average of 125 g were exposed to Toddy (24.5 ml/body weight/day) and ethanol (0.52 ml/kg body weight/day) for 15 days before conception and throughout gestation. On the 19th day of gestation, altered liver function and hyperlipidemia was seen in both the treated groups. Altered liver function was evidenced by the increased activity of alcohol dehydrogenase, aldehyde dehydrogenase, glutamic oxaloacetic transaminase or aspartate amino transferase (GOT), glutamic pyruvic transaminase or alanine amino transferase (GPT) and gamma glutamyl transpeptidase (GGT). Hyperlipidemia was caused by increased biosynthesis and decreased degradation of lipids. The incorporation of 14C acetate in lipids and activities of HMG CoA reductase and lipogenic enzymes were elevated and activity of LPL and bile acids contents were decreased. Toddy treated rats were more severely affected than those receiving an equivalent quantity of ethanol. Toddy seemed to potentiate the toxicity induced by alcohol indicating the role of the nonethanolic portion. Hepatic functions were also affected.
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PMID:Effect of exposure to a country liquor (Toddy) during gestation on lipid metabolism in rats. 1131 2

A high level of physical activity is associated with a lower cardiovascular risk in adult and elderly subjects. Several mechanisms are involved. Physical activity induces an increase in energy output. The contribution of fats to muscle energy metabolism increases with exercise duration. It decreases with exercise intensity. EPOC contributes by about 10% to the total energy cost of exercise. This supplementary energy expenditure is principally covered with fat oxidation, this being related to GH release. Part of energy expended during intermittent exercise is supplied by fat oxidation. The used lipids are taken from the muscular triacylglycerol stores and from the circulating FFA and lipoprotein triacylglycerols. Hydrolysis of triacylglycerols is achieved by LPL. Endurance training induces an increased contribution from fat to the exercise energy need. This results from increased muscle capillary density, enhanced activity of LPL and of the enzymes controlling beta-oxydation. The increased energy expenditure results in a reduced fat mass, which accounts for a decreased plasma triacylglycerol level. Endurance activity requiring approximately an expenditure of 60 kJ.kg-1 per week usually produces favourable lipoprotein changes. Level of post-prandial lipemia is lowered. These alterations disappear within the first two days of recovery.
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PMID:[Lipid metabolism and exercise]. 1150 66

Accumulating evidences in recent major clinical studies have shown the importance of anti-hyperlipidemic treatment in preventing atherosclerotic cardiovascular diseases. Lipid-lowering drugs can be divided into HMG-CoA reductase inhibitors (statins), bile-acid sequestrants (resins), nicotinic acid, fibrates and probucol. Among them, statins had revolutionary impact on the treatment of hyperlipidemia since pravastatin, which was developed in Japan, was launched in 1989. Several lipid-lowering drugs are now under development in Japan, including pitavastatin, rosuvastatin, F-1394 (ACAT inhibitor), CS-505 (ACAT inhibitor) and NO-1886 (LPL activator). In this review, characteristics of these new lipid-lowering drugs will be discussed.
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PMID:[Lipid-lowering drugs]. 1177 57

The disturbance of lipid metabolism is seen in some inherited diseases and also in patients with some kinds of underlying diseases. The presence of its disturbance can be detected by measuring the concentrations of cholesterol and triglyceride in serum. Although hyperlipidemia or hypolipidemia is the result of abnormal lipid metabolism, hyperlipidemia is of more concern to physicians because of the close association with atherosclerosis. Responsible genes for some primary (or hereditary) hyperlipidemic diseases have been confirmed as follows; LPL or apo C-II for primary chylomicronemia, LDL receptor for familial hypercholesterolemia and apo B-100 for familial defective apo B-100. However, the responsible gene remains controversial for familial combined hyperlipidemia, though AI/CIII/AIV cluster is one of the possible candidate genes. Secondary hyperlipidemia is caused by various diseases such as diabetes mellitus, renal diseases and cholestasis. This type of hyperlipidemia is improved by therapy for the underlying diseases. To date, the mechanism of lipid metabolism has been defined in a molecular basis. In fact, sterol regulatory element-binding protein (SREBP), peroxisome proliferator-activated receptor (PPAR) and ATP-binding cassette transporter subfamily A, member 1(ABCA1) were recently identified and it was demonstrated that these regulate lipid metabolism.
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PMID:[Disturbance of lipid metabolism]. 1198 47

Apolipoprotein C-I (apoC-I) has been proposed to act primarily via interference with apoE-mediated lipoprotein uptake. To define actions of apoC-I that are independent of apoE, we crossed a moderately overexpressing human apoC-I transgenic, which possesses a minimal phenotype in the WT background, with the apoE-null mouse. Surprisingly, apoE-null/C-I mice showed much more severe hyperlipidemia than apoE-null littermates in both the fasting and non-fasting states, with an almost doubling of cholesterol, primarily in IDL+LDL, and a marked increase in triglycerides; 3-fold in females to 260 +/- 80 mg/dl and 14-fold in males to 1409 +/- 594 mg/dl. HDL lipids were not significantly altered but HDL were apoC-I-enriched and apoA-II-depleted. Production rates of VLDL triglyceride were unchanged as was the clearance of post-lipolysis remnant particles. Plasma post-heparin hepatic lipase and lipoprotein lipase levels were undiminished as was the in vitro hydrolysis of apoC-I transgenic VLDL. However, HDL from apoC-I transgenic mice had a marked inhibitory effect on hepatic lipase activity, as did purified apoC-I. LPL activity was minimally affected. Atherosclerosis assay revealed significantly increased atherosclerosis in apoE-null/C-I mice assessed via the en face assay. Inhibition of hepatic lipase may be an important mechanism of the decrease in lipoprotein clearance mediated by apoC-I.
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PMID:Overexpression of apoC-I in apoE-null mice: severe hypertriglyceridemia due to inhibition of hepatic lipase. 1245 76

Dyslipidaemia is common in patients with Type 2 diabetes and is held to be responsible for considerable CVD-related morbidity and mortality. Patients with Type 2 diabetes are at high risk from complications associated with atherosclerosis and should therefore receive preventive interventions. At the level of the adipocyte, impaired insulin action leads to increased rates of intracellular hydrolysis of triglycerides with the release of NEFA. The rise in NEFA provides substrate for the liver that, in the presence of impaired insulin action and relative insulin deficiency, is associated with complex alterations in plasma lipids: * Plasma VLDL levels are raised. (i). Increased VLDL levels are associated with post-prandial hyperlipidaemia that is compounded by impaired LPL activity. The latter may be independently associated with CAD. (ii). Remnant particles can deliver more cholesterol to macrophages than LDL-C particles. Thrombogenic alterations in the coagulation system also ensue from hypertriglyceridaemia. * Plasma HDL-C levels are reduced. (i). The reduction in cardioprotective HDL-C means a reduction of cholesterol efflux from the tissues--the first step in reverse cholesterol transport to the liver from peripheral tissues. (ii). The antioxidant and antiatherogenic activities of HDL-C are reduced when circulating levels are low. * LDL-C particles become small and dense. Small, dense LDL-C particles are held to be more atherogenic than their larger, buoyant counterparts because they (a) are more liable to oxidation and (b) may more readily adhere to and subsequently invade the arterial wall. The atherogenicity of LDL-C may also be enhanced by nonenzymatic glycation. Metabolic and lipid abnormalities can often be improved with lifestyle changes, including dietary modification, weight loss, smoking cessation and increased exercise. Although attainment of better glycaemic control may improve diabetic dyslipidaemia, pharmacological intervention is usually required. Several large-scale clinical trials, including 4S and more recently HPS, have clearly demonstrated the benefits of statins in reducing cardiovascular events. By virtue of their high absolute risk of CVD, many patients with Type 2 diabetes may achieve a greater risk reduction than their non-diabetic counterparts. For example, in 4S there was a 43% reduction in total mortality risk among patients with diabetes compared with 29% for non-diabetics and a reduced risk of MI by 55% vs. 32% for diabetic and non-diabetics, respectively. In the diabetic subgroup in HPS, there were reductions of approximately 25-30% in the risk of first major vascular events. More recently, the lipid-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was halted early because of a significant reduction in cardiovascular events compared with placebo. Surprisingly an analysis of subgroups failed to show significance among the diabetic population, although the sample size, shortened follow-up period and higher drop-in statin use among diabetics on placebo may have affected results. The Collaborative Atorvastatin Diabetes Study (CARDS), involving 2800 patients with Type 2 diabetes, was halted 2 years early in June 2003 because patients allocated atorvastatin had significant reductions in MI, stroke and surgical procedures compared with those receiving placebo. The UKPDS demonstrated that the appearance and progression of certain microvascular complications of Type 2 diabetes could be reduced by treatment directed at hyperglycaemia and hypertension. In addition, correction of dyslipidaemia in patients with diabetes is important in reducing the high toll from macrovascular disease. The subjects in the HPS had similar lipid profiles to the participants in UKPDS, suggesting that additional benefit would accrue from a therapeutic assault on the main cardiovascular risk factors simultaneously. We now have firm evidence that appropriate use of statins in patients with Type 2 diabetes can significantly reduce cardiovascular morbidity and mortality.
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PMID:Lipoprotein abnormalities and their consequences for patients with type 2 diabetes. 1498 18

Studies in humans and mice have shown that increased expression of apolipoprotein C-I (apoC-I) results in combined hyperlipidemia with a more pronounced effect on triglycerides (TGs) compared with total cholesterol (TC). The aim of this study was to elucidate the main reason for this effect using human apoC-I-expressing (APOC1) mice. Moderate plasma human apoC-I levels (i.e., 4-fold higher than human levels) caused a 12-fold increase in TG, along with a 2-fold increase in TC, mainly confined to VLDL. Cross-breeding of APOC1 mice on an apoE-deficient background resulted in a marked 55-fold increase in TG, confirming that the apoC-I-induced hyperlipidemia cannot merely be attributed to blockade of apoE-recognizing hepatic lipoprotein receptors. The plasma half-life of [3H]TG-VLDL-mimicking particles was 2-fold increased in APOC1 mice, suggesting that apoC-I reduces the lipolytic conversion of VLDL. Although total postheparin plasma LPL activity was not lower in APOC1 mice compared with controls, apoC-I was able to dose-dependently inhibit the LPL-mediated lipolysis of [3H]TG-VLDL-mimicking particles in vitro with a 60% efficiency compared with the main endogenous LPL inhibitor apoC-III. Finally, purified apoC-I impaired the clearance of [3H]TG-VLDL-mimicking particles independent of apoE-mediated hepatic uptake in lactoferrin-treated mice. Therefore, we conclude that apoC-I is a potent inhibitor of LPL-mediated TG-lipolysis.
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PMID:Severe hypertriglyceridemia in human APOC1 transgenic mice is caused by apoC-I-induced inhibition of LPL. 1557 44

Adenovirus-mediated overexpression of human apolipoprotein E (apoE) induces hyperlipidemia by stimulating the VLDL-triglyceride (TG) production rate and inhibiting the LPL-mediated VLDL-TG hydrolysis rate. Because apoC-III is a strong inhibitor of TG hydrolysis, we questioned whether Apoc3 deficiency might prevent the hyperlipidemia induced by apoE overexpression in vivo. Injection of 2 x 10(9) plaque-forming units of AdAPOE4 caused severe combined hyperlipidemia in Apoe-/- mice [TG from 0.7 +/- 0.2 to 57.2 +/- 6.7 mM; total cholesterol (TC) from 17.4 +/- 3.7 to 29.0 +/- 4.1 mM] that was confined to VLDL/intermediate density lipoprotein-sized lipoproteins. In contrast, Apoc3 deficiency resulted in a gene dose-dependent reduction of the apoE4-associated hyperlipidemia (TG from 57.2 +/- 6.7 mM to 21.2 +/- 18.5 and 1.5 +/- 1.4 mM; TC from 29.0 +/- 4.1 to 16.4 +/- 9.8 and 2.3 +/- 1.8 mM in Apoe-/-, Apoe-/-.Apoc3+/-, and Apoe-/-.Apoc3-/- mice, respectively). In both Apoe-/- mice and Apoe-/-.Apoc3-/- mice, injection of increasing doses of AdAPOE4 resulted in up to a 10-fold increased VLDL-TG production rate. However, Apoc3 deficiency resulted in a significant increase in the uptake of TG-derived fatty acids from VLDL-like emulsion particles by white adipose tissue, indicating enhanced LPL activity. In vitro experiments showed that apoC-III is a more specific inhibitor of LPL activity than is apoE. Thus, Apoc3 deficiency can prevent apoE-induced hyperlipidemia associated with a 10-fold increased hepatic VLDL-TG production rate, most likely by alleviating the apoE-induced inhibition of VLDL-TG hydrolysis.
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PMID:ApoC-III deficiency prevents hyperlipidemia induced by apoE overexpression. 1586 38

To elucidate abnormalities of LPL gene in hyperlipidemia in the Chinese population in Guangdong,genomic DNA was extracted from leukocyte of 258 patients with primary hyperlipidemia.A segment of LPL gene including exon 4 and its flanking sequences was analyzed by PCR-SSCP. The PCR products with abnormal SSCP pattern were cloned and sequenced. As a C-->T transition mutation at-6 bp of intron 3 was found in two Chinese with hyperlipidemia and the mutation was not found in 252 normolipidemic controls,the C-->T transition in intron 3 may be related to hyperlipedemia.
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PMID:[Variants of exon 4 and its flanking region of LPL Gene in patients with hyperlipidemia]. 1613 40

Our study evaluated the relationship between the pathologic changes associated with atherosclerosis, as primarily represented by postprandial remnant-like lipoproteins and carotid intima-media thickness (IMT), in type 2 diabetic patients. Meal tolerance tests (MTT) were performed in 68 patients with type 2 diabetes. The subjects were divided by pre-meal and 2-h postprandial triglyceride (TG) levels into the normotriglyceridemia (NTG) group; the postprandial hypertriglyceridemia (PHTG) group; and the fasting hypertriglyceridemia (FHTG) group. HOMA-R values were significantly higher in the FHTG group than in the NTG group, with the plasma pre-heparin LPL mass and serum adiponectin levels in the FHTG and PHTG groups significantly lower than in the NTG group. One- and two hour postprandial RLP-TG levels were significantly higher in the PHTG group than in the NTG group, while there was no significant difference in postprandial glucose levels between the two groups. The IMT values were significantly higher in both the FHTG and PHTG groups than in the NTG group. Logistics regression analysis of the 1- and 2-h RLP-TG values using IMT as an induced variable showed the odds ratio for high IMT values to be 5.17 (p < 0.05) for the 1-h RLP-TG values and 3.01 (p = 0.105) for the 2-h RLP-TG values. Our study results suggest that delayed TG metabolism leading to the retention of remnants in type 2 diabetic patients appears to be closely associated with atherosclerosis, and that postprandial hyperlipidemia is an independent risk factor for the early onset of atherosclerosis.
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PMID:Association between postprandial remnant-like particle triglyceride (RLP-TG) levels and carotid intima-media thickness (IMT) in Japanese patients with type 2 diabetes: assessment by meal tolerance tests (MTT). 1638 88


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