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)

An experimental model was explored for the study of the effect of thyroid hormone on lipid transport and metabolism in the rat. The development of the hypothyroid state was accompanied by an early decrease in free fatty acids (FFA) followed by an increase in the level of cholesterol and a decrease in triglyceride concentration. Simultaneously, the adipose tissue lipoprotein lipase activity increased while the lecithin-cholesterol acyltransferase was unchanged. The hypothyroid state was also accompanied by a decrease in the concentrations of tryglycerides and cholesterol in very low density lipoproteins (VLDL) while the 2 lipids increased in the low density lipoprotein (LDL) fraction. Administration of triiodothyronine markedly reduced the amount of cholesterol in both the LDL and high density lipoprotein (HDL) fractions. The animal model has been shown to have similarities with findings in human subjects.
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PMID:Lipid transport in the hypothyroid rat as reflected by the serum concentrations of free fatty acids, lipoproteins, lecithin-cholesterol acyltransferase and lipoprotein lipase activity in adipose tissue. 724 Jun 72

It has been shown previously that dietary fat type influences body fat accumulation in rats. The effects of dietary fat type on serum thyroid hormone, activity of Na+,K(+)-ATPase and lipoprotein lipase were studied. Rats were fed an experimental diet containing lard, high oleic safflower oil, safflower oil or linseed oil for 12 wk. Carcass fat content was significantly higher in rats fed the lard diet than in those fed the other diets. However, intra-abdominal adipose tissue weights were not affected by type of dietary fat. The serum triiodothyronine concentration and the activity of Na+,K(+)-ATPase in the liver and skeletal muscle were significantly lower in the lard diet group than in the other diet groups. The lipoprotein lipase activity of abdominal subcutaneous fat was significantly higher in rats fed the lard diet than in rats fed the other diets, but the activity of lipoprotein lipase in intra-abdominal fat was not significantly different. These results suggest that the intake of lard, compared with the intake of the vegetable oils, may decrease Na+,K(+)-ATPase activity in the liver and skeletal muscle by lowering serum triiodothyronine concentration, resulting in the promotion of body fat accumulation.
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PMID:Serum triiodothyronine concentration and Na+,K(+)-ATPase activity in liver and skeletal muscle are influenced by dietary fat type in rats. 766 54

Administration of streptozotocin (100 mg/kg) to adult Sprague-Dawley rats reduced both functional (heparin releasable) lipoprotein lipase activity in perfused hearts and total and heparin-releasable lipoprotein lipase activity in isolated cardiomyocytes, and produced a hypothyroid state (decreased plasma levels of triiodothyronine and thyroxine). Administration of replacement doses of triiodothyronine (3 or 10 micrograms/kg for 3 days) to diabetic rats normalized heparin-releasable lipoprotein lipase activity in perfused hearts, but the depressed lipoprotein lipase activity in cardiomyocytes from diabetic hearts was unchanged by in vivo thyroid hormone treatment. However, hypothyroidism in thyroidectomized rats did not alter lipoprotein lipase activity in either perfused hearts or isolated cardiomyocytes. Therefore, thyroid hormones may interact with some other factor(s) in this acute, insulin-deficient model of diabetes to selectively regulate functional, heparin-releasable lipoprotein lipase activity in perfused hearts.
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PMID:Regulation of myocardial lipoprotein lipase activity by diabetes and thyroid hormones. 776 64

A new member of the low density lipoprotein receptor gene family that binds and internalizes very low density lipoprotein (VLDL) particles was previously cloned and characterized from the rabbit and human. The physiological role of this putative VLDL receptor is not known, but its tissue distribution and ligand specificity suggest a possible role in the delivery of triglycerides to peripheral tissue. To learn more about the potential function of this receptor, we measured the changes in VLDL receptor mRNA and protein in various tissues following dietary or hormonal manipulation of rats. No significant changes in the VLDL receptor mRNA or protein were seen after a 48-h fast and subsequent to refeeding. A striking change in receptor mRNA and protein was observed in skeletal muscle of hypothyroid and hyperthyroid rats. In hypothyroid rats, the amount of immunodetectable VLDL receptor was reduced by 80%, while in the hyperthyroid animals it was increased by 300%. These maneuvers did not affect VLDL receptor mRNA or protein levels in adipose tissue or heart. The changes in VLDL receptor mRNA in muscle were opposite to those observed with lipoprotein lipase. These studies suggest that the VLDL receptor plays a role in a metabolic process in muscle that is regulated by thyroid hormone.
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PMID:Regulation of the very low density lipoprotein receptor by thyroid hormone in rat skeletal muscle. 792 62

Dyslipidaemia may be treated with a number of safe and effective pharmacological agents that target specific lipid disorders through a variety of mechanisms. The bile-acid sequestrants--cholestyramine and colestipol--primarily decrease LDL cholesterol by binding bile acids, thereby decreasing intrahepatic cholesterol, and by increasing the activity of LDL receptors. Nicotinic acid lowers LDL cholesterol and triglyceride by decreasing VLDL synthesis and by decreasing free fatty acid mobilization from peripheral adipocytes. The HMG-CoA reductase inhibitors--fluvastatin, lovastatin, pravastatin and simvastatin--lower LDL cholesterol by partially inhibiting HMG-CoA reductase (the rate-limiting enzyme of cholesterol biosynthesis) and by increasing the activity of LDL receptors. The fibric-acid derivatives--bezafibrate, ciprofibrate, clofibrate, fenofibrate and gemfibrozil--primarily decrease triglyceride by increasing lipoprotein lipase activity and by decreasing the release of free fatty acids from peripheral adipose tissue. Probucol decreases LDL cholesterol by increasing non-receptor-mediated LDL clearance; as an anti-oxidant, probucol also decreases LDL oxidation; oxidized LDL which is thought to lead to atherogenesis. Although these agents have been proven safe in clinical trials, like any drug, they carry the risk for adverse effects. The bile-acid sequestrants may cause constipation, reflux oesophagitis, and dyspepsia, and may bind coadministered medications such as digitalis glycosides, beta blockers, warfarin, and exogenous thyroid hormone. Nicotinic acid use is commonly associated with flushing and pruritus and may also cause non-specific gastrointestinal complaints, hepatotoxicity (hepatic necrosis, hepatitis, or elevated liver enzymes), gout, myolysis, decreased glucose tolerance and increased fasting glucose levels, and ophthalmological complications including decreased visual acuity, toxic amblyopia, and cystic maculopathy. The HMG-CoA reductase inhibitors may produce liver enzyme elevations, creatine kinase elevations and rhabdomyolysis. The combination of a reductase inhibitor and a fibrate increases the risk for rhabdomyolysis. Possible adverse effects of the fibric-acid derivatives include abdominal discomfort, nausea, flatulence, increased lithogenicity of bile, liver enzyme elevations and creatine kinase elevations. Probucol may increase the QTc interval and may cause non-specific gastrointestinal complaints.
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PMID:Currently available hypolipidaemic drugs and future therapeutic developments. 859 27

The relation of plasma lipids and pseudocholinesterase (PChE) activity was studied in rats made hypothyroid by treatment with propylthiouracil (0.05% in drinking water for 28 days) and in hypothyroid patients prior and after L-thyroxine-therapy (1. week 25-50 microg, 2.-4. week 100 microg daily). In rats, thyroid hormone deficiency caused a significant increase in plasma and adipose tissue PChE activity as well as total plasma cholesterol (TC) concentration, and a decrease in plasma triglyceride (TG) concentration. In contrast to rats, thyroid-deficient humans demonstrated a decrease in plasma PChE activity and an increase in both TC and TG, in comparison with euthyroid controls. After one month's therapy with L-thyroxine, reversion of PChE activity and lipid concentrations occurred. The opposite changes of PChE elicited by thyroid hormone deficiency in men and rats are similar to the respective changes in lipoprotein lipase (LPL) activity, observed by other authors. The inverse correlation between both PChE and LPL activity and TG concentration suggests that PChE, similarly to LPL, may be involved in TG hydrolysis.
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PMID:The relation between plasma lipid levels and pseudocholinesterase activity in hypothyroidism. 956 55

To investigate the effect of thyroid dysfunction on high-density lipoprotein (HDL) metabolism, we measured HDL subfractions, apolipoprotein A-I containing particles (LpA-I and LpA-I:A-II), and the activities of enzymes involved in the remodeling and metabolism of HDL [namely hepatic lipase (HL), lipoprotein lipase, and cholesteryl ester transfer protein (CETP)] in 18 hyperthyroid and 17 hypothyroid patients before and after treatment. HDL was subfractionated by density gradient ultracentrifugation, and LpA-I was analyzed by electroimmunodiffusion. The major changes were found in the HDL2 subfraction and in LpA-I particles. HDL2-C and LpA-I were reduced in hyperthyroidism (P < 0.01, P < 0.05, respectively) and increased in hypothyroidism (both P < 0.05) compared with their respective euthyroid matched controls. Changes in HDL2-cholesterol were reversed after treatment in both hyper- and hypothyroid patients, and LpA-I also decreased in the hypothyroid patients after treatment. HL (P < 0.05) and CETP activities (P < 0.05) were elevated in hyperthyroidism and reduced in hypothyroidism (P < 0.05, P < 0.01 respectively) and both were related to free T4 levels. The changes in HDL2-C and LpA-I correlated significantly with changes in HL after treatment but not with CETP or lipoprotein lipase. In summary, HDL metabolism was altered in thyroid dysfunction, and the effect of thyroid hormone on HDL was mediated mainly via its effect on HL activity.
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PMID:Effect of thyroid dysfunction on high-density lipoprotein subfraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein. 970 70

Mice deficient for all known thyroid hormone receptors, TRalpha1-/-beta-/- mice, display a clear skeletal phenotype characterized by growth retardation, delayed maturation of long bones and decreased trabecular and total bone mineral density (BMD; -14.6 +/- 2.8%, -14.4 +/- 1.5%). The aim of the present study was to investigate the molecular mechanisms behind the skeletal phenotype in TRalpha1-/-beta-/- mice. Global gene expression analysis was performed on total vertebrae from wild-type (WT) and TRalpha1-/-beta-/- mice using DNA microarray and the results were verified by real-time PCR. The mRNA levels of six genes (AdipoQ, Adipsin, Fat-Specific Protein 27 (FSP 27), lipoprotein lipase (LPL), retinol-binding protein (RBP) and phosphoenolpyruvate carboxykinase (PEPCK)) expressed by mature adipocytes were increased in TRalpha1-/-beta-/- compared with WT mice. An increased amount of fat (225% over WT) due to an increased number but unchanged mean size of adipocytes in the bone marrow of TRalpha1-/-beta-/- mice was revealed. Interestingly, the mRNA levels of the key regulator of osteoclastogenesis, receptor activator of NF-varkappab ligand (RANKL), were dramatically decreased in TRalpha1-/-beta-/- mice. In conclusion, TRalpha1-/-beta-/- mice demonstrated increased expression of adipocyte specific genes and an increased amount of bone marrow fat. Thus, these mice have increased adipogenesis in bone marrow associated with decreased trabecular bone mineral density (BMD). One may speculate that these effects either could be caused by an imbalance in the differentiation of the osteoblast and the adipocyte lineages at the expense of osteoblastogenesis, or by independent effects on the regulation of both osteoblastogenesis and adipogenesis.
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PMID:Increased adipogenesis in bone marrow but decreased bone mineral density in mice devoid of thyroid hormone receptors. 1578 Sep 76

Thyroid hormone (T3) and peroxisome proliferators have overlapping metabolic effects in the maintenance of lipid homeostasis. Their actions are mediated by their respective receptors: thyroid hormone receptors (TR) and peroxisome proliferator-activated receptors (PPAR). We recently found that a dominantly negative TRbeta mutant (PV) that causes a genetic disease, resistance to thyroid hormone, acts to repress the ligand (troglitazone)-mediated transcriptional activity of PPARgamma in cultured thyroid cells. This finding suggests that TRbeta mutants could crosstalk with PPARgamma-signaling pathways. The present study explored the molecular mechanisms by which PV represses the PPARgamma transcriptional activity. Gel-shift assays show that the PV, similar to wild-type TRbeta, bound to the peroxisome proliferator response element (PPRE) as homodimers and heterodimers with PPARgamma or the retinoid X receptor (RXR), thereby competing with PPARgamma for binding to PPRE and for sequestering RXR. Association of PPRE-bound PV with corepressors [e.g., nuclear receptor corepressor (NCoR)] that led to transcriptional repression was independent of T3 and troglitazone. Chromatin immunoprecipitation assay further demonstrated that, despite the presence of ligands, NCoR was recruited to PPRE-bound PV on a PPARgamma-target gene, the lipoprotein lipase, in vivo, suggesting the dominant action of PV on PPARgamma-mediated transcriptional activity. Thus, the dominant negative action of PV is not limited on the wild-type TRs. The findings that TRbeta mutants affect PPARgamma functions through dominant negative action provide insights into the molecular mechanisms by which TR regulates the PPARgamma-target genes involved in metabolic pathways, lipid homeostasis, and carcinogenesis.
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PMID:Thyroid hormone receptor beta mutants: Dominant negative regulators of peroxisome proliferator-activated receptor gamma action. 1626 Jul 19

Late term fetuses from genetically obese dams have slightly larger fat cells, greater adipose tissue lipoprotein lipase (LPL) activities, elevated levels of thyroid hormones, and depressed growth hormone (GH) levels when compared to fetuses from lean dams. We have investigated the influence of thyroid hormone and GH status per se on these and other adipose tissue traits by chronically treating hypophysectomized (hypox) fetuses (day 70) between day 90 and 105 of gestation with either thyroxine (T4) or human GH. Treatment with T4 decreased body weights (P<.05), increased serum T4 levels (P<.05), and enhanced skin and hair development (P<.05). Quantitative analysis of sections of perirenal and subcutaneous adipose tissue indicated that T4 increased LPL activity (P<.05), slightly increased fat cell size, and more than doubled (P<.05) lipid accretion. A hypox induced deficit in fat cell cluster number in the outer layer of subcutaneous tissue was normalized by T4 (P<.05). Conversely, human GH (hGH) treatment had no influence on body weight, increased serum hGH levels, decreased fat cell size (P<.05) and LPL activity (P<.05) but had no influence on lipid accretion. Quantitative analysis of adipose tissue sections provided direct and indirect evidence of a "critical" or "sensitive" period between 90 and 105 days, since fetal hypox at day 70 severely impeded preadipocyte recruitment/replication during this period. Furthermore, T4 but not GH effectively normalized this hypox-induced deficiency in preadipocyte development. Therefore, T4 may have a major role in preadipocyte recruitment/replication during late fetal life.
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PMID:The influence of human growth hormone (GH) and thyroxine (T4) on the differentiation of adipose tissue in the fetus. 1635 May 85


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