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)

These studies were conducted to determine the effects of exercise training on plasma lipoprotein levels and metabolism in the guinea pig to evaluate potential utilization of this model for studies of exercise-mediated effects on the regulation of sterol and lipoprotein metabolism and atherosclerosis regression. Male guinea pigs (n = 5 per group) were randomly assigned to either a control or an exercise group. The exercise protocol consisted of a 7-week training program, 5 days/wk on a rodent treadmill. Final speed and duration were 33 meters/min for 30-40 min per session. Guinea pigs in the exercise group had 33% lower plasma triacylglycerol concentrations (P < 0.01), 66% higher HDL cholesterol levels (P < 0.05) and 31% lower plasma free fatty acids (P < 0.05) than guinea pigs from the non-exercised group. In addition, lipoprotein lipase activity in the heart was 50% higher (P < 0.025) in guinea pigs allocated to the exercise protocol. Exercise training resulted in modifications in composition and size of lipoproteins. The concentrations of free cholesterol in LDL and HDL were higher in the exercised guinea pigs. The LDL peak density values were lower in guinea pigs from the exercise group compared to controls suggesting that exercise training resulted in larger LDL particles. In contrast, no significant effects due to exercise were observed in hepatic cholesterol concentrations, hepatic HMG-CoA reductase activity or LDL binding to guinea pig hepatic membranes. These data indicate that exercise had a more pronounced effect on the intravascular processing of lipoproteins than on hepatic cholesterol metabolism. In addition, the pattern of changes in guinea pig lipoprotein metabolism, in response to exercise training, was similar to reported effects in humans.
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PMID:Exercise improves plasma lipid profiles and modifies lipoprotein composition in guinea pigs. 1255 59

Statins and fibrates constitute the two major families of hypolipidaemic drugs. Statins are widely used in the treatment of patients with pure hypercholesterolaemias and mixed dyslipidaemias while fibrates are used to treat hypertriglyceridaemias and mixed hyperlipidaemias. Some fibrates efficiently reduce low density-lipoprotein (LDL)-cholesterol. Statins inhibit HMG-CoA reductase and decrease cellular cholesterol synthesis. The resulting lower intracellular cholesterol concentrations suppress the capacity of Insing-1 and Insing-2 to inhibit the interaction of SCAP with SREBP-2 in the membrane of the endoplasmic reticulum and the formation of the SCAP: SREBP-2:SP-1 complex. When formed, this complex migrates towards the Golgi where activated SP-1 and SP-2 protease cleave SREBP-2 to give a free NH2-terminal-SREBP-2 peptide which migrates towards the nucleus. In the nucleus, this free NH2-terminal-SREBP-2 peptide binds to the SRE contained in the promoter of the gene of the LDL(B/E)-receptor and induces the transcription of this gene, and the over-expression of the LDL(B/E)-receptor in the cytoplasmic plasma membrane of hepatocytes. The over-expression of the LDL-receptor in the liver increases the clearance of circulating LDL, decreasing the LDL-cholesterol plasma levels. Fibrates decrease plasma triglycerides by decreasing their hepatic synthesis and increasing their catabolism. They decrease the triglyceride-very low density-lipoprotein (VLDL) synthesis through their capacity to increase the beta-oxidation of fatty acids in the liver. They increase the plasma triglyceride catabolism by inducing the lipoprotein lipase gene transcription and decreasing the apoC-III gene transcription. Fibrates increase high density-lipoprotein (HDL)-cholesterol by increasing apoA-I and apoA-II gene transcription. These bio-molecular effects of fibrates are entirely due to their capacity to activate PPAR alpha and to induce the over expression of genes containing a PPRE in their promoter. Therefore, the mechanism of action of the statins and fibrates depends on their capacity to modulate the expression of genes controlling the lipoprotein metabolism.
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PMID:[Mechanisms of actions of statins and fibrates]. 1282 95

Statins and fibrates constitute the two major families of lipid-lowering agents. Statins are widely used for the treatment of pure hypercholesterolaemia while fibrates are used for the treatment of hypertriglyceridemia. Both drugs are also used for the treatment of mixed dyslipidemia. Some fibrates efficiently lower serum LDL-cholesterol. Statins inhibit HMG-CoA reductase and decrease cellular cholesterol synthesis. The resulting lower intracellular cholesterol concentration induces the activation of SREBP thus inducing the over expression and transcription of the LDL receptor gene. This over expression of the LDL receptor in the liver increases the clearance of circulating LDL thus decreasing the LDL-cholesterol plasma levels. The effects of fibrates on lipid metabolism are entirely due to their capacity to activate PPAR-alpha and to induce the over expression of genes containing a PPRE in their promoter. Fibrates decrease triglyceride concentrations by increasing the beta-oxidation of fatty acids in the liver and by decreasing triglyceride-VLDL synthesis. Fibrates also decrease triglycerides by increasing the hydolysys of triglycerides in chylomicron and VLDL through their capacity to increase and to decrease the lipoprotein lipase and the apo C-III transcription, respectively. Fibrates could decrease triglycerides partly by inducing apo A-V over-expression. These molecules increase HDL-cholesterol by increasing apo A-I and apo A-II transcription. Therefore the mechanisms of action of statins and fibrates depend on their capacity to modulate the expression of genes controlling lipoprotein metabolism.
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PMID:[Anti-cholesterol agents, new therapeutic approaches]. 1474 68

Alcoholics usually suffer from malnutrition and are especially deficient in micronutrients like vitamin C, selenium and Zn. In the present study, combined effects of selenium and ascorbic acid on alcohol-induced hyperlipidemia were studied in guinea pigs. Four groups of male guinea pigs were maintained for 45 days as follows: control (1 mg ascorbate (AA)/100 g body mass/day), ethanol (900 mg ethanol/100 g body mass + 1 mg AA/100 g body mass/day), selenium+ascorbic acid [(25 mg AA + 0.05 mg Se)/100 g body mass/day], ethanol+selenium+ascorbic acid [(25 mg AA + 0.05 mg Se + 900 mg ethanol)/100 g body mass/day]. Co-administration of selenium and ascorbic acid along with alcohol reduced the concentration of all lipids, as also evidenced from the decreased activities of hydroxymethylglutaryl-CoA reductase and enhanced activities of plasma lecithin cholesterol acyl transferase and lipoprotein lipase. Concentrations of bile acids were increased. We conclude that the supplementation of Se and ascorbic acid reduced alcohol induced hyperlipidemia, by decreased synthesis and increased catabolism.
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PMID:Combined effect of selenium and ascorbic acid on alcohol induced hyperlipidemia in male guinea pigs. 1505 Sep 22

We are continuing to both elucidate underlying mechanisms and identify clinical applications for a chemically induced murine model of dose-controlled hyperlipidemia and atherosclerosis. This murine model neither utilizes genetically modified mice nor a high-fat, cholate-containing diet, although simultaneous ingestion of a high-fat, cholate-enriched diet potentiates the hyperlipidemic response and the number and size of aortic atherosclerotic lesions formed in C57BL/6 mice. The chemical agent used to induce hyperlipidemia is poloxamer 407 (P-407), a nonionic surface-active-agent. To date, we have investigated the effect of P-407 on the biologic activity of a variety of key enzymes involved with lipid metabolism and transport. These enzymes include 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, lipoprotein lipase (LPL), cholesterol 7alpha-hydoxylase (C7alphaH), sterol 27-hydroxylase (S27H), lecithin cholesterol acyltransferase (LCAT), cholesteryl-ester-transfer-protein (CETP), hepatic lipase (HL), and endothelial lipase (EL). P-407 directly inhibits the heparin-releasable fraction of LPL and HL and indirectly increases the biologic activity of CETP and LCAT. Long-term (> 4 months) administration of P-407 to C57BL/6 mice appears to have no effect on the biologic activity of S27H and HMG-CoA reductase, but decreases the activity of C7alphaH. This would suggest that hypertriglyceridemia and hypercholesterolemia result from inhibition of LPL and C7alphaH, respectively, while the biologic activity of CETP and LCAT are indirectly increased to compensate for the increased cholesterol burden. The above model has proven useful for predicting the therapeutic efficacy of existing and possibly newer statin drugs, as well as evaluating the potential of one statin drug (atorvastatin calcium) to cause the regression of P-407-induced atherosclerotic lesions in mice. The P-407-induced murine model of atherogenesis represents an alternative to the use of either genetically modified or diet-induced models and may also prove beneficial for the evaluation of newer classes of antihyperlipidemic agents such as antioxidants, CETP inhibitors, and liver X receptor (LXR) agonists.
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PMID:The P-407-induced murine model of dose-controlled hyperlipidemia and atherosclerosis: a review of findings to date. 1508 72

The prevalence of obesity has become increasingly common worldwide, in particular western countries. Obesity, together with insulin resistance, leads to metabolic syndrome in which other coronary risk factors including hyperlipidemia and hypertension cluster in one individual. Hyperlipidemia in metabolic syndrome is characterized increased triglyceride(TG), decreased HDL-C, and small dense LDL, called dyslipidemic triad. Dyslipidemia is attributable to increased flux of free fatty acids to the liver, which promotes TG synthesis, thus VLDL production. Increased VLDL, together with decreased lipoprotein lipase activity due to insulin resistance, causes accumulation of TG-rich lipoproteins, including proatherogenic remnants. Further, increased activities of cholesteryl ester transfer protein and hepatic triglyceride lipase results in low HDL-C and small dense LDL. Initial treatment should be directed to modify life style(weight loss and increased physical activity). Then, pharmacological intervention should be considered when the initial treatment is not fully successful. Fibrate derivatives are considered to be ideal to correct dyslipidemic triad. In addition, potent statins(HMG-CoA reductase inhibitor) can be alternative in metabolic syndrome subjects with elevated LDL-C levels.
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PMID:[Dyslipidemia in metabolic syndrome]. 1520 47

Male albino rats were given ethanol (3.76 g/kg body weight/day) to induce hyperlipidemia. The rats showed increased concentration of cholesterol and triglycerides in the serum and tissues. Inclusion of coconut protein and L-arginine into ethanol fed rats produced lower levels of total cholesterol, LDL+ VLDL cholesterol, triglycerides and atherogenic index in the serum. Concentration of tissue cholesterol and triglycerides was also lower in these groups. Administration of coconut protein and L-arginine in the ethanol fed rats caused decreased activity of HMG-CoA reductase in the liver and increased activity of lipoprotein lipase in the heart. The activities of malic enzyme and glucose-6-phosphate dehydrogenase were also lower in these groups. Feeding coconut protein and L-arginine in ethanol treated rats showed increased concentration of hepatic bile acids and fecal excretion of neutral sterols and bile acids. All these effects were comparable in rats fed coconut protein and those fed L-arginine. These observations indicate that the major factor responsible for the hypolipidemic effect of coconut protein is due to the high content of L-arginine.
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PMID:Influence of coconut kernel protein on lipid metabolism in alcohol fed rats. 1527 81

Several murine models demonstrate that mammalian longevity can be increased by single gene mutations affecting endocrine signalling, particularly via the GH/IGF-1 axis. In this study, we identify age-independent patterns of hepatic gene expression characteristic of long-lived Snell (Pit1(dw/dwJ)) dwarf mice. Comparative microarray analysis of young and aged male livers was performed to discover specific genes differentially expressed between Pit1(dw/dwJ) and control mice. Further examination by real-time RT-PCR confirmed that transcripts encoding HMG-CoA synthase-1, HMG-CoA reductase, farnesyl diphosphate synthase, isopentenyl pyrophosphate isomerase, mevalonate decarboxylase, squalene epoxidase, lanosterol demethylase, malic enzyme and apolipoprotein A-IV were significantly decreased in both male and female Pit1(dw/dwJ) livers at 3-5 and 24-28 months of age. In contrast, transcripts encoding the beta(3)-adrenergic receptor, lipoprotein lipase, PPAR gamma and a very low-density lipoprotein receptor homologue were increased significantly in dwarf livers relative to age-matched controls. These studies reveal enduring transcriptional changes characteristic of Pit1(dw/dwJ) dwarf mice that involve genes regulating cholesterol biosynthesis, fatty acid metabolism and lipoprotein homeostasis. Linked to global energy metabolism, this stable shift in hepatic gene expression may contribute to longevity determination by influencing particular metabolic functions often compartmentalized within the mitochondrion and peroxisome; further this metabolic shift may also parallel many transcriptional changes induced by caloric restriction.
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PMID:Altered cholesterologenic and lipogenic transcriptional profile in livers of aging Snell dwarf (Pit1dw/dwJ) mice. 1537 52

Although elevated low-density lipoprotein (LDL)-cholesterol is a well established coronary heart disease (CHD) risk factor, the ability to adequately discriminate high-risk individuals by this risk factor alone is limited and other metabolic risk variables are known to modulate CHD risk. For instance, it has been reported that the cluster of metabolic disturbances observed among individuals with abdominal obesity, the so-called metabolic syndrome, is associated with a substantially increased risk of CHD. Among the features of the dyslipidaemic profile observed in these individuals, the high triglyceride-low high-density lipoprotein (HDL)-cholesterol dyslipidaemia is predictive of an elevated risk of CHD. Fibric acid derivatives (fibrates) have been used in clinical practice for more than 2 decades as a class of agents known to decrease triglyceride levels while substantially increasing HDL-cholesterol levels, with a limited but significant additional lowering effect on LDL-cholesterol levels. Although the clinical benefits of HMG-CoA reductase inhibitors (statins) have been well documented by primary and secondary prevention trials that justify their widespread use, it was not until the publication of the VA-HIT (Veterans Affairs High-Density Lipoprotein Intervention Trial) that the relevance of identifying HDL-cholesterol as a therapeutic target to reduce the risk of recurrent CHD events was finally confirmed. The clinical benefits of fibrate therapy are especially important in the subpopulation of patients with low HDL-cholesterol levels with the metabolic syndrome, particularly in patients with type 2 diabetes mellitus or in abdominally obese, hyperinsulinaemic patients. Evidence also suggests that there is a 'fibrate effect' that mediates the reduction in CHD risk beyond the favourable impact of these agents on HDL-cholesterol levels. This last notion is consistent with the pleiotropic effects of fibrates which are known to be related to their mechanisms of action. Through peroxisome proliferator-activated alpha-receptors, fibrates have a significant impact on the synthesis of several apolipoproteins (apo) and enzymes of lipoprotein metabolism as well as on the expression of several genes involved in fibrinolysis and inflammation. Fibrate therapy has been reported to decrease apo CIII levels (a powerful inhibitor of lipoprotein lipase) and increase apo AI levels, as well as to increase lipoprotein lipase activity. Such changes contribute to improve the catabolism of triglyceride-rich lipoproteins, leading to a substantial increase in HDL-cholesterol levels accompanied by a shift in the size and density of LDL particles (from small, dense LDL particles to larger, more buoyant cholesteryl ester-rich LDL). It is proposed that some of these pleiotropic effects could explain some of the clinical benefits of fibrate therapy beyond its HDL-raising properties, particularly among patients with abdominal obesity, hyperinsulinaemia or type 2 diabetes with both low HDL- and low/normal LDL-cholesterol levels.
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PMID:Role of fibric acid derivatives in the management of risk factors for coronary heart disease. 1545 34

To determine whether changes in plasma lipids following a weight loss program were related to modifications in gene expression of the LDL receptor (LDL-R), lipoprotein lipase (LPL), and 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, overweight/obese premenopausal women were recruited. The 10-wk, randomized, double-blind intervention consisted of a hypoenergetic diet, high in protein (30% energy) and low in carbohydrate (40% energy), increased physical activity (number of steps taken per day), and intake of a supplement (carnitine or placebo). Our initial hypothesis was that carnitine would enhance the beneficial effects of weight loss on plasma lipids and anthropometrics. Because the carnitine and placebo groups did not differ in any of the measured variables, data for all subjects were pooled and comparisons were made between baseline and postintervention. Mean weight loss was 4.4 kg (P < 0.001), and plasma triglycerides (TG), total, and LDL cholesterol (LDL-C) were reduced by 31.8, 9.9, and 11.9%, respectively (P < 0.001). The expression of the genes of interest was measured in RNA extracted from mononuclear cells at baseline and postintervention using a semiquantitative RT-PCR method. Glyceraldehyde-3-phosphate dehydrogenase was used as an internal control. After 10 wk, there was a 25.7% increase in the abundance of LPL mRNA (P < 0.01) and a 27.7% increase in that of LDL-R mRNA (P < 0.01). The expression of HMG-CoA reductase was not altered by weight loss. The results suggest that the increased expression of the LDL-R and LPL after the intervention might have contributed to the lower plasma LDL-C and TG observed in these women.
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PMID:The lowering of plasma lipids following a weight reduction program is related to increased expression of the LDL receptor and lipoprotein lipase. 1579 26


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