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)

Lipid and lipoprotein disorders are frequently detected in insulin dependent diabetics, which predisposes the high cardiovascular risk present in these patients. Studies performed with insulin dependent children showed early changes in lipid metabolism, usually correlated and aggravated by poor glycemic control. However, there are abnormalities present even in diabetic children with good glycemic control. The usual measures used to improve diabetic control are not sufficient to correct all the lipid disorders in Diabetes Mellitus. Hyperglycemia is the major factor, inducing metabolic lipid changes by increasing hepatic synthesis of triglycerides and promoting lipoprotein and apolipoprotein glycosylation and oxidation. Other changes, associated with the decrease of lipoprotein lipase activity are directly related to insulin deficiency. The lipid profile in children with poor diabetic control is similar to that already described for adult patients. The main abnormalities found are: increased levels of triglycerides, VLDL-Tg, LDL-Tg, VLDL-Cholesterol, Apo B and Apo CIII, with decreased values of HDL-Cholesterol and Apo AI. As there is a strong correlation between control and the degree of lipid changes, even with normal levels of cholesterol and triglycerides, measurements of Apo AI, Apo B100 and Apo CIII seem to be good and reliable indicators of glycemic control in diabetic children, and a factor with high predictive value for the evaluation of cardiovascular risk in adult patients.
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PMID:[Lipid disorders in children with insulin-dependent diabetes mellitus]. 985 17

Overexpression of the adipocyte differentiation and determination factor-1 (ADD-1) or sterol regulatory element binding protein-1 (SREBP-1) induces the expression of numerous genes involved in lipid metabolism, including lipoprotein lipase (LPL). Therefore, we investigated whether LPL gene expression is controlled by changes in cellular cholesterol concentration and determined the molecular pathways involved. Cholesterol depletion of culture medium resulted in a significant induction of LPL mRNA in the 3T3-L1 preadipocyte cell line, whereas addition of cholesterol reduced LPL mRNA expression to basal levels. Similar to the expression of the endogenous LPL gene, the activity of the human LPL gene promoter was enhanced by cholesterol depletion in transient transfection assays, whereas addition of cholesterol caused a reversal of its induction. The effect of cholesterol depletion upon the human LPL gene promoter was mimicked by cotransfection of expression constructs encoding the nuclear form of SREBP-1a, -1c (also called ADD-1) and SREBP-2. Bioinformatic analysis demonstrated the presence of 3 potential sterol regulatory elements (SRE) and 3 ADD-1 binding sequences (ABS), also known as E-box motifs. Using a combination of in vitro protein-DNA binding assays and transient transfection assays of reporter constructs containing mutations in each individual site, a sequence element, termed LPL-SRE2 (SRE2), was shown to be the principal site conferring sterol responsiveness upon the LPL promoter. These data furthermore underscore the importance of SRE sites relative to E-boxes in the regulation of LPL gene expression by sterols and demonstrate that sterols contribute to the control of triglyceride metabolism via binding of SREBP to the LPL regulatory sequences.
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PMID:Induction of LPL gene expression by sterols is mediated by a sterol regulatory element and is independent of the presence of multiple E boxes. 1109 Feb 77

Traditional risk factors for coronary artery disease (CAD) predict about 50% of the risk of developing CAD. The Adult Treatment Panel (ATP) III has defined emerging risk factors for CAD, including small, dense low-density lipoprotein (LDL). Small, dense LDL is often accompanied by increased triglycerides (TGs) and low high-density lipoprotein (HDL). An increased number of small, dense LDL particles is often missed when the LDL cholesterol level is normal or borderline elevated. Small, dense LDL particles are present in families with premature CAD and hyperapobetalipoproteinemia, familial combined hyperlipidemia, LDL subclass pattern B, familial dyslipidemic hypertension, and syndrome X. The metabolic syndrome, as defined by ATP III, incorporates a number of the components of these syndromes, including insulin resistance and intra-abdominal fat. Subclinical inflammation and elevated procoagulants also appear to be part of this atherogenic syndrome. Overproduction of very low-density lipoproteins (VLDLs) by the liver and increased secretion of large, apolipoprotein (apo) B-100-containing VLDL is the primary metabolic characteristic of most of these patients. The TG in VLDL is hydrolyzed by lipoprotein lipase (LPL) which produces intermediate-density lipoprotein. The TG in intermediate-density lipoprotein is hydrolyzed further, resulting in the generation of LDL. The cholesterol esters in LDL are exchanged for TG in VLDL by the cholesterol ester tranfer proteins, followed by hydrolysis of TG in LDL by hepatic lipase which produces small, dense LDL. Cholesterol ester transfer protein mediates a similar lipid exchange between VLDL and HDL, producing a cholesterol ester-poor HDL. In adipocytes, reduced fatty acid trapping and retention by adipose tissue may result from a primary defect in the incorporation of free fatty acids into TGs. Alternatively, insulin resistance may promote reduced retention of free fatty acids by adipocytes. Both these abnormalities lead to increased levels of free fatty acids in plasma, increased flux of free fatty acids back to the liver, enhanced production of TGs, decreased proteolysis of apo B-100, and increased VLDL production. Decreased removal of postprandial TGs often accompanies these metabolic abnormalities. Genes regulating the expression of the major players in this metabolic cascade, such as LPL, cholesterol ester transfer protein, and hepatic lipase, can modulate the expression of small, dense LDL but these are not the major defects. New candidates for major gene effects have been identified on chromosome 1. Regardless of their fundamental causes, small, dense LDL (compared with normal LDL) particles have a prolonged residence time in plasma, are more susceptible to oxidation because of decreased interaction with the LDL receptor, and enter the arterial wall more easily, where they are retained more readily. Small, dense LDL promotes endothelial dysfunction and enhanced production of procoagulants by endothelial cells. Both in animal models of atherosclerosis and in most human epidemiologic studies and clinical trials, small, dense LDL (particularly when present in increased numbers) appears more atherogenic than normal LDL. Treatment of patients with small, dense LDL particles (particularly when accompanied by low HDL and hypertriglyceridemia) often requires the use of combined lipid-altering drugs to decrease the number of particles and to convert them to larger, more buoyant LDL. The next critical step in further reduction of CAD will be the correct diagnosis and treatment of patients with small, dense LDL and the dyslipidemia that accompanies it.
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PMID:Clinical relevance of the biochemical, metabolic, and genetic factors that influence low-density lipoprotein heterogeneity. 1241 79

Current strategies for both the primary and secondary prevention of coronary heart disease (CHD) focus on the traditional risk factors, such as hypertension, smoking cessation, and cholesterol, as the primary determinants of the cardiac risk profile, with particular emphasis on the reduction of low-density lipoprotein cholesterol (LDL-C) to targeted goal levels as endorsed by the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). Large primary and secondary prevention trials with the hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) have demonstrated varying reductions in cardiovascular events associated with similar changes in LDL-C levels, suggesting statins may possess additional beneficial effects on other risk factors. Retrospective analyses of many statin trials have evaluated the association between several polymorphic candidate genes (apolipoprotein E, stromelysin-1, beta-fibrinogen, cholesteryl ester transfer protein, lipoprotein lipase, hepatic lipase, and platelet glycoprotein III) which have been identified as predictors of disease severity and both metabolic and clinical response to statin therapy. These results suggest that statin therapy improves plasma lipid profiles in all patients, but preferentially benefits individuals who carry a high risk, variant genotype for these risk factors as compared to individuals with the wild-type genotype. These observations suggest that determining individual patient genotype may be useful in optimizing the benefits of statin therapy. These hypothesis-generating data need to be prospectively evaluated in genotyped patients.
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PMID:Genetic polymorphisms in emerging cardiovascular risk factors and response to statin therapy. 1284 89

Epidemiological studies have shown a positive association of colon cancer with hyperlipidemia. Furthermore, signaling generated by peroxisome proliferator-activated receptor (PPAR) alpha and gamma ligands, suggested to be candidate tumor preventive agents, has been shown to lower serum triglyceride levels. In the present study, we assessed hyperlipidemia in Apc-deficient mice, model animals for human familial adenomatous polyposis, and examined the effects of pioglitazone and bezafibrate, respectively, PPARgamma and PPARalpha agonists, on both hyperlipidemia and intestinal polyposis. Serum lipid levels in Apc(1309) mice and Min mice from 6 to 15 weeks of age were measured. Although serum levels of triglyceride and cholesterol were low in both Apc(1309) and wild-type mice at 6 weeks, triglycerides were elevated 10-fold in Apc(1309) mice by the age of 12 weeks but not in their wild-type counterparts. Cholesterol was also increased significantly, and marked centrilobular-restricted steatosis was observed in the livers of aged Apc(1309) mice. Similar findings were observed for Min mice at 15 weeks of age. Moreover, lipoprotein lipase mRNA levels in the liver and small intestine of Apc(1309) and Min mice were demonstrated to be lower than those in wild-type mice. Treatment of Apc(1309) mice with 100 and 200 ppm pioglitazone or bezafibrate for 6 weeks from 6 weeks of age caused dose-dependent reduction in serum triglycerides and cholesterol, along with reduction in the numbers of intestinal polyps to 67% of the control value. The present study clearly demonstrated a hyperlipidemic state in Apc gene-deficient mice and a potential of PPARalpha and PPARgamma ligands to suppress both hyperlipidemia and polyp formation. Hyperlipidemia in these mice may thus be associated with their intestinal lesion development.
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PMID:Concomitant suppression of hyperlipidemia and intestinal polyp formation in Apc-deficient mice by peroxisome proliferator-activated receptor ligands. 1452 40

Cholesterol feeding upregulates CYP7A1 in rats but downregulates CYP7A1 in rabbits. To clarify the mechanism responsible for the upregulation of CYP7A1 in cholesterol-fed rats, the effects of dietary cholesterol (Ch) and cholic acid (CA) on the activation of the nuclear receptors, liver X-receptor (LXR-alpha) and farsenoid X-receptor (FXR), which positively and negatively regulate CYP7A1, were investigated in rats. Studies were carried out in four groups (n = 12/group) of male Sprague-Dawley rats fed regular chow (control), 2% Ch, 2% Ch + 1% CA, and 1% CA alone for 1 wk. Changes in mRNA expression of short heterodimer partner (SHP) and bile salt export pump (BSEP), target genes for FXR, were determined to indicate FXR activation, whereas the expression of ABCA1 and lipoprotein lipase (LPL), target genes for LXR-alpha, reflected activation. CYP7A1 mRNA and activity increased twofold and 70%, respectively, in rats fed Ch alone when the bile acid pool size was stable but decreased 43 and 49%, respectively, after CA was added to the Ch diet, which expanded the bile acid pool 3.4-fold. SHP and BSEP mRNA levels did not change after feeding Ch but increased 88 and 37% in rats fed Ch + CA. This indicated that FXR was activated by the expanded bile acid pool. When Ch or Ch + CA were fed, hepatic concentrations of oxysterols, ligands for LXR-alpha increased to activate LXR-alpha, as evidenced by increased mRNA levels of ABCA1 and LPL. Feeding CA alone enlarged the bile acid pool threefold and increased the expression of both SHP and BSEP. These results suggest that LXR-alpha was activated in rats fed both Ch or Ch + CA, whereas CYP7A1 mRNA and activity were induced only in Ch-fed rats where the bile acid pool was not enlarged such that FXR was not activated. In rats fed Ch + CA, the bile acid pool expanded, which activated FXR to offset the stimulatory effects of LXR-alpha on CYP7A1.
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PMID:Dietary cholesterol stimulates CYP7A1 in rats because farnesoid X receptor is not activated. 1468 80

Sixty-seven male patients with hypercholesterolemia, divided into three groups according to apolipoprotein E phenotype (33 with apoE3/ 3 phenotype, E3 group; 23 with 2/2 or 2/3, E2+ group; 11 with 4/4 or 4/3, E4+ group), received daily 20-40 mg of fluvastatin for 12 weeks. The levels of triglyceride (TG), cholesterol (Chol), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) were measured after 0, 4, 8 and 12 weeks on fluvastatin and after 4 weeks washout period. Lipid percentage changes (delta) were not associated with apoE phenotype for any treatment time. Cholesterol decreased by 14% after 12 weeks and HDL-C increased by 14-16% after 12 weeks for three phenotype groups. deltaTG, deltaChol, deltaLDL-C were associated positively, while negatively for deltaHDL-C, with the corresponding basal lipid values for the three groups. The positive deltaTG values occurred at a low basal TG0 level and became negative at TG0 > 1.6-1.9 mM. For E3 and E4+ groups, only a single parameter contributed significantly into a variation of lipid percentage changes. For the E2+ group, TG0 and Chol0 contributed in a reciprocal manner into deltaTG12/0, both positively into deltaChol8/0; Chol0 and HDL-C0 both negatively contributed into deltaHDL-C12/0. HDL-C0 contributed reciprocally into LDL-C variability for E2+ and E4+ groups. Three effects seem to contribute differently into lipid response among patients with different apoE phenotype: the inhibition of hepatic and lipoprotein lipase activities, the competition between TG-rich and low-density lipoproteins for LDL-receptor and the accumulation of intermediate-density lipoproteins in patients bearing E2 isoform.
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PMID:Time-dependent lipid response on fluvastatin therapy of patients with hypercholesterolemia sensitive to apoE phenotype. 1525 90

This study investigated the effect of administration of alpha-lipoic acid (LA) on lipid metabolism in high fructose-fed insulin-resistant rats. High-fructose feeding (60 g/100 g diet) to normal rats resulted in a significant increase in the concentrations of cholesterol, triglycerides (TGs), free fatty acids (FFAs), and phospholipids in plasma, liver, kidney, and skeletal muscle. Reduced activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) and increased activity of the lipogenic enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase were observed in plasma and liver. High-density lipoprotein cholesterol (HDL-C) was significantly lowered and very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated. Treatment with LA (35 mg/kg body weight intraperitoneal) reduced the effects of fructose. The rats showed near-normal levels of lipid components on plasma and tissues. Activities of key enzymes of lipid metabolism were also restored to normal values. Cholesterol distribution in the plasma lipoproteins was normalized, resulting in a favorable lipid profile. This study demonstrates that LA can alter lipid metabolism in fructose-fed insulin-resistant rats and may have implications in the treatment of insulin resistance.
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PMID:Effect of alpha-lipoic acid on lipid profile in rats fed a high-fructose diet. 1551 87

Magnesium deficiency and excess sucrose in the diet have been shown to play an important role in the development of insulin resistance. In the present study we have looked at the combined effect of a low magnesium high sucrose diet on basal glucose and insulin levels, erythrocyte insulin receptors and lipid profile in rats. For this purpose rats were divided into four groups and fed control, low magnesium, high sucrose and low magnesium high sucrose diets respectively for three months. The biochemical analysis showed a significant increase in blood glucose and triglyceride levels after one, two and three months of feeding in both the high sucrose and the low magnesium high sucrose groups, while rats fed a low magnesium diet showed a significant increase in blood glucose and triglyceride levels only after the second month. Insulin levels increased significantly in low magnesium, high sucrose and low magnesium high sucrose groups by the end of the study period. Compared to control rats, the binding of insulin to the erythrocyte insulin receptors was reduced significantly in the high sucrose and the low magnesium high sucrose groups. Cholesterol levels were found to increase significantly in the high sucrose group at the end of one month and three months of feeding. HDL-cholesterol decreased significantly in the low magnesium high sucrose group by the end of the study. Serum and RBC magnesium levels demonstrated a significant decrease in the low magnesium and the low magnesium high sucrose groups. The post heparin plasma lipoprotein lipase activity was decreased significantly in low magnesium, high sucrose and low magnesium high sucrose groups compared to control rats. These findings suggest that feeding a diet low in magnesium and high in sucrose causes insulin resistance in rats.
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PMID:Studies on the development of an insulin resistant rat model by chronic feeding of low magnesium high sucrose diet. 1572 5

Cholesterol and phospholipid concentrations in serum lipoproteins, plasma activities of lecithin:cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) and lipoprotein lipase (LPL) activity in adipose tissue biopsies were measured ante and post partum in dairy cows given either free or restricted access to feed during the dry period. After parturition, all cows were fed ad libitum. The purpose of this study was to try to understand the earlier observed marked drop post partum in plasma triacylglycerol (TAG) in terms of lipoprotein metabolism in cows developing fatty liver post partum. As would be expected, free access to feed during the dry period induced a rise of hepatic TAG concentrations post partum associated with a decrease in plasma TAG levels. Total and free cholesterol concentrations in the VLDL, IDL, LDL and HDL2 fractions fell immediately after parturition. VLDL and IDL cholesterol concentrations remained at a constant, low level during the entire sampling period post partum, whereas the drop in LDL and HDL2 cholesterol post partum was followed by a rebound rise. Plasma LCAT and PLTP activities decreased by on average 19% and 33%, respectively, after parturition and then rose to values seen before parturition, but there was no effect of feeding regimen during the dry period. Activities of LCAT and PLTP were significantly correlated with cholesterol and phospholipid concentrations in LDL and HDL2. Plasma LCAT activity, as measured with exogenous substrate, and PLTP activity were both positively correlated with HDL3 phospholipid levels. LPL activity in adipose tissue dropped after parturition, the drop being smaller after feeding ad libitum during the dry period. It is concluded that the drop in adipose tissue LPL activity post partum is at variance with the simultaneous fall in plasma TAG. Possibly, the decrease in adipose tissue LPL activity helps to channel fatty acids away from adipose tissue into the udder. The post-partum changes in lipid transfer proteins in the blood are in line with the changes observed in the levels of the lipoproteins.
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PMID:Fatty liver in dairy cows post partum is associated with decreased concentration of plasma triacylglycerols and decreased activity of lipoprotein lipase in adipocytes. 1590 77


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