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)

A severe hyperlipemia in mink, with a pattern that suggested recessive inheritance, was observed at a farm in Norway. On a normal mink diet, affected animals had grossly elevated levels of plasma triglycerides which decreased towards normal on a low-fat diet. Normal minks had the main part of their plasma cholesterol in the HDL fraction. Affected minks, although severely hypertriglyceridaemic, had almost normal levels of both LDL and HDL. Affected minks frequently had lipogranulomas in the mesentery and the pancreas. The lipogranulomatous tissue contained spaces filled with an amorphous, sudanophilic substance with many foamy macrophages in the fibrous tissue between the lesions. Separation of postheparin plasma on heparin-agarose revealed that the affected minks had no detectable lipoprotein lipase activity but normal activity of hepatic lipase. Both normal and affected minks had inactive lipoprotein lipase protein in pre- and post-heparin plasma. This protein, which eluted before the active lipase from heparin-agarose, probably corresponds to lipase monomers. The presence of lipoprotein lipase mass in the affected minks, but no activity, indicates that there might be a point mutation in the lipase gene. The minks provide a new animal model for studies on pancreatitis induced by hypertriglyceridemia and on lipoprotein metabolism in the lipoprotein lipase-deficient state and show features similar to those found in human hyperlipoproteinemia type I.
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PMID:Lipoprotein lipase deficiency with pancreatitis in mink: biochemical characterization and pathology. 918 2

We studied the determinants of postprandial lipemia in 49 post-coronary-bypass men with low HDL cholesterol (< or = 1.1 mmol/l at screening). The subjects were given a mixed meal containing 63 g fat and 150,000 IU vitamin A. Serum was obtained before and 3, 4, 5, 6, and 8 h after the meal. S(f) > 400 and S(f) 12-400 lipoproteins, LDL, and HDL were separated by ultracentrifugation; and triglyceride (TG), retinyl ester (RE), and apolipoprotein (apo)E concentrations were measured. The associations of 15 potential predictor variables with measures of postprandial lipemia were evaluated in univariate and multivariate models. Fasting TG concentration was the most important determinant of postprandial lipid and apoE concentrations. In univariate analyses, neither apoE phenotype nor common genetic polymorphisms in the apoB gene (XbaI and apoB signal peptide length polymorphisms), lipoprotein lipase gene (Hind III polymorphism), or apoC-III gene (C[1100] to T sequence change) significantly predicted the magnitude of postprandial lipemia. In multivariate linear regression analyses, fasting TG concentration (P< 0.001) and postheparin plasma hepatic lipase activity (P = 0.023) were directly, and body mass index (P = 0.007) and the presence of apoE2 (P = 0.029) allele inversely related to the TG increment in S(f) >400 lipoproteins. Fasting TG was associated with a high (P < 0.001) and presence of the SP24 allele of the apoB signal peptide gene with a low (P = 0.014) S(f) 12-400 TG response. Fasting TG concentrations alone predicted 35%, 10%, and 34% of the variability in postprandial S(f) >400 responses of TG, RE, and apoE; multivariate models improved this predictive power to 40-50%. Even multivariate models were poor predictors of postprandial responses in S(f) 12-400 lipoproteins (0-26%). Much of the interindividual variation in the magnitude of postprandial lipemia remained unexplained in the present study.
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PMID:Determinants of postprandial lipemia in men with coronary artery disease and low levels of HDL cholesterol. 925 71

People with non-insulin-dependent diabetes mellitus (NIDDM) have a higher incidence of cardiovascular disease (CVD) than the non-diabetic population. In addition, NIDDM patients have a spectrum of lipid abnormalities that may confer an increased risk of developing CVD. The pattern of dyslipidaemia seen in NIDDM patients is different from that seen in the non-diabetic population. This suggests that patients with NIDDM may need different lipid-lowering treatment from that used in the non-diabetic population. In the post-absorptive state, secretion of very low-density lipoprotein (VLDL) is higher in patients with NIDDM, possibly because of the impaired ability of insulin to inhibit lipolysis and to reduce hepatic VLDL secretion. Clearance of triglyceride-rich lipoproteins is also important in determining the extent of postprandial hyperlipidaemia. Lipoprotein lipase (LPL) reduces plasma lipoprotein concentration via several mechanisms. In patients with NIDDM, the capacity of LPL to minimize postprandial hyperlipidaemia may be reduced, although the pathophysiological basis of this is not known. Other changes in patients with NIDDM, such as modifications to cholesteryl ester transfer protein (CETP) and hepatic lipase activity, may also affect postprandial lipaemia but such effects are probably secondary to alterations in lipoprotein clearance. Present evidence suggests that postprandial hyperlipidaemia is atherogenic. There are, however, little specific data from patients with NIDDM. More studies are therefore needed to establish the optimal treatment of dyslipidaemia in patients with NIDDM.
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PMID:Postprandial lipoproteins in non-insulin-dependent diabetes mellitus. 927 17

Polymerized hemoglobin solutions (Hb-based oxygen carriers; HBOCs) and a second-generation perfluorocarbon (PFC) emulsion (Perflubron) are in clinical trials as temporary oxygen carriers ("blood substitutes"). Plasma and serum samples from patients receiving HBOCs look markedly red, whereas those from patients receiving PFC appear to be lipemic. Because hemolysis and lipemia are well-known interferents in many assays, we examined the effects of these substances on clinical chemistry, immunoassay, therapeutic drug, and coagulation tests. HBOC concentrations up to 50 g/L caused essentially no interference for Na, K, Cl, urea, total CO2, P, uric acid, Mg, creatinine, and glucose values determined by the Hitachi 747 or Vitros 750 analyzers (or both) or for immunoassays of lidocaine, N-acetylprocainamide, procainamide, digoxin, phenytoin, quinidine, or theophylline performed on the Abbott AxSym or TDx. Gentamycin and vancomycin assays on the AxSym exhibited a significant positive and negative interference, respectively. Immunoassays for TSH on the Abbott IMx and for troponin I on the Dade Stratus were unaffected by HBOC at this concentration. Tests for total protein, albumin, LDH, AST, ALT, GGT, amylase, lipase, and cholesterol were significantly affected to various extents at different HBOC concentrations on the Hitachi 747 and Vitros 750. The CK-MB assay on the Stratus exhibited a negative interference at 5 g/L HBOC. HBOC interference in coagulation tests was method-dependent-fibrometer-based methods on the BBL Fibro System were free from interference, but optical-based methods on the MLA 1000C exhibited interferences at 20 g/L HBOC. A 1:20 dilution of the PFC-based oxygen carrier (600 g/L) caused no interference on any of these chemistry or immunoassay tests except for amylase and ammonia on the Vitros 750 and plasma iron on the Hitachi 747.
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PMID:Effect of hemoglobin- and Perflubron-based oxygen carriers on common clinical laboratory tests. 929 68

Transgenic rabbits were produced that expressed high plasma levels (30-70 mg/dl) of human apolipoprotein (apo) E2(Cys-158), an apoE variant associated with the human genetic disorder type III hyperlipoproteinemia (HLP). Male transgenic rabbits fed normal chow had up to 8-fold (289 +/- 148 mg/dl) and 15-fold (697 +/- 452 mg/dl) increases in plasma total cholesterol and triglycerides, respectively, compared with nontransgenic males. Female transgenic rabbits had only a modest hyperlipidemia (total cholesterol, 140 +/- 46 mg/dl; total triglycerides, 174 +/- 66 mg/dl). Both sexes displayed the hallmarks fo type III HLP: beta-migrating very low density lipoproteins (beta-VLDL) (intestinal and hepatic remnant lipoproteins) and significantly increased VLDL and intermediate density lipoproteins. Apolipoprotein E2-containing VLDL particles were cleared from teh circulation more slowly and were more resistant to lipoprotein lipase-mediated lipolysis than normal VLDL. Only females had increased high density lipoproteins (HDL) (40%), which were shifted from typical small HDL to larger HDL1. Plasma apoE2 was predominantly associated with beta-VLDL in males and with HDL in females. To ascertain reasons for the phenotypic gender difference, we treated male transgenic rabbits with 17alpha-ethinyl estradiol. Estrogen treatment for 10 days dramatically decreased total cholesterol (73%) and triglycerides (89%) and converted beta-VLDL to pre-beta-migrating VLDL. Concomitantly, lipoprotein lipase and hepatic lipase activities increased by 90%, low density lipoprotein receptor activity was stimulated significantly, apoE2 was redistributed to HDL, and HDL were converted to HDL1. Conversely, ovariectomy in female transgenic rabbits significantly increased total cholesterol (75%), triglycerides (117%), and beta-VLDL, while decreasing lipoprotein lipase and hepatic lipase activities by 35% and redistributing apoE2 to the beta-VLDL. Thus, estrogen status appears to be responsible for much of the gender difference of the lipoprotein phenotype, mainly by modulating both lipase and low density lipoprotein receptor activities. Furthermore, transgenic rabbits fed normal chow for 11 months developed fatty streaks, and some had more advanced atherosclerotic lesions, especially around the aortic arch and proximal abdominal aorta. The lesions were more extensive in males, roughly correlating with the magnitude of the hyperlipidemia. Therefore, high plasma levels of human apoE2 in transgenic rabbits result in a type III HLP phenotype, in which males have both more severe hyperlipidemia and more extensive atherosclerosis than females.
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PMID:Apolipoprotein E2 transgenic rabbits. Modulation of the type III hyperlipoproteinemic phenotype by estrogen and occurrence of spontaneous atherosclerosis. 931 50

Chylomicrons are formed in the intestine and transport dietary triglyceride to peripheral tissues and cholesterol to the liver. The enzyme lipoprotein lipase, with apolipoprotein (apo)C-II as a co-factor, hydrolyzes chylomicron triglyceride allowing the delivery of free fatty acids to muscle and adipose tissue. As a result, a new particle called a chylomicron remnant is formed. This particle is enriched in cholesteryl ester and fat-soluble vitamins and contains apoB-48 and apoE. It is rapidly removed from the circulation by the liver. ApoE is the moiety required for rapid hepatic removal. Its activity is inhibited by C apolipoproteins, especially apoC-I. Hepatic removal appears to be accomplished by several overlapping mechanisms. The particle must first achieve a size that allows it to be "sieved" through the endothelial fenestre allowing entrance into the space of Disse. Here, it may 1) be removed directly by LDL receptors; 2) acquire additional apoE that is secreted free into the space, and then be removed directly by the LDL receptor-related protein (LRP); or 3) it may be sequestered in the space. Sequestration occurs by binding of apoE to heparan sulfate proteoglycans and/or binding of apoB to hepatic lipase. Sequestered particles may be further metabolized allowing apoE, and lysophospholipid enrichment, followed by transfer to one of the above receptors for hepatic uptake. The above formulation is based upon animal studies. In humans, delayed removal of chylomicron remnants has been documented in diabetes, renal failure, and familial combined hyperlipemia and is the abnormality resulting in type III hyperlipidemia. Case control studies have identified delayed remnant removal as an independent risk factor for atherosclerotic cardiovascular disease. Thus, understanding the further details of the processes, and how it can be regulated in humans, is an important challenge for the future.
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PMID:Hepatic uptake of chylomicron remnants. 939 16

Infection, inflammation and trauma induce marked changes in the plasma levels of a wide variety of proteins (acute phase response), and these changes are mediated by cytokines. The acute phase response is thought to be beneficial to the host. The host's response to injury also results in dramatic alterations in lipid metabolism and circulating lipoprotein levels which are mediated by cytokines. A large number of cytokines including TNF, the interleukins, and the interferons increase serum triglyceride levels. This rapid increase (1-2 h) is predominantly due to an increase in hepatic VLDL secretion while the late increase may be due to a variety of factors including increased hepatic production of VLDL or delayed clearance secondary to a decrease in lipoprotein lipase activity and/or apolipoprotein E levels on VLDL. In animals other than primates, cytokines also increase serum cholesterol levels, most likely by increasing hepatic cholesterol. Cytokines increase hepatic cholesterol synthesis by stimulating HMG CoA reductase gene expression and decrease hepatic cholesterol catabolism by inhibiting cholesterol 7 alpha-hydroxylase, the key enzyme in bile acid synthesis. Injury and/or cytokines also decrease HDL cholesterol levels and induce alterations in the composition of HDL. The content of SAA and apolipoprotein J increase, apolipoprotein A1 may decrease, and the cholesterol ester content decreases while free cholesterol increases. Additionally, key proteins involved in HDL metabolism are altered by cytokines; LCAT activity, hepatic lipase activity, and CETP levels decrease. These changes in lipid and lipoprotein metabolism may be beneficial in a number of ways including: lipoproteins competing with viruses for cellular receptors, apolipoproteins neutralizing viruses, lipoproteins binding and targeting parasites for destruction, apolipoproteins lysing parasites, redistribution of nutrients to cells involved in the immune response and/or tissue repair, and lipoproteins binding toxic agents and neutralizing their harmful effects. Thus, cytokines induce marked changes in lipid metabolism that lead to hyperlipidemia which represents part of the innate immune response and may be beneficial to the host.
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PMID:Beneficial effects of cytokine induced hyperlipidemia. 955 31

The individual benefits of dietary therapy for hyperlipidaemia are known to be unpredictable. Variants at the lipoprotein lipase gene have been shown to associate with atherogenic lipoprotein phenotypes and the delayed clearance of triglyceride-rich lipoproteins. Together with variants of the closely homologous hepatic lipase gene, these may influence the extent of amelioration of plasma lipoprotein concentrations seen in dyslipidaemic patients treated with a low saturates/low cholesterol diet. We correlated the lipid changes seen following an 8-week diet in 83 subjects with primary hypercholesterolaemia (fasting plasma cholesterol > 6.5 mmol/L) with alleles of three restriction polymorphisms (LPL-Hind III and Pvu II; HL-Msp I). Although dietary changes produced a significant improvement in fasting lipids [total cholesterol falling by 5.2% (range -27.9% to +24.3%) and low-density lipoprotein cholesterol reduced by 6.0% (-30.5% to +29.3%)], no significant difference in response between different genotypes could be detected.
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PMID:Dietary treatment of hypercholesterolaemia: lack of relationship between individual response and genetic variation at the lipase loci. The Fluvastatin Genotyping Group. 963 11

This study was designed to examine the role of somatostatin in regulating changes in lipid metabolism of larvae and metamorphosing landlocked sea lamprey, Petromyzon marinus. Larvae and animals in late metamorphosis (stage 6 on a 7-stage scale) were injected intraperitoneally once per day for 2 days with either saline (0.6%) or somatostatin-14 (SS-14; 500 ng/g body wt). Injection of SS-14 into larval and stage 6 metamorphosing animals resulted in elevated plasma fatty acids levels. In larvae, SS-14-induced hyperlipidemia was supported by enhanced lipolysis, as indicated by increased triacylglycerol lipase (TGL) activity in the liver and kidney. Mobilization of larval renal lipid was accompanied by reduced TG synthesis, as indicated by decreased diacylglycerol acyltransferase (DGAT) activity. In stage 6 metamorphosing lamprey, SS-14 did not significantly affect TGL activity; however, SS-14 significantly reduced fatty acid synthesis, as measured by acetyl-CoA carboxylase activity, in kidney, liver, and muscle, as well as muscular TG synthesis. SS-14-stimulated lipid depletion is reminiscent of the pattern of lipid metabolism displayed by P. marinus during their spontaneous metamorphosis-an observation which suggests that somatostatin may play a role in metamorphosis-associated changes in lipid metabolism in this species.
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PMID:Effects of somatostatin on lipid metabolism of larvae and metamorphosing landlocked sea lamprey, Petromyzon marinus. 967 89

Mice lacking hepatic lipase have been reported to express mild hyperlipidemia characterized by increased concentrations of large high density lipoproteins, but normal concentrations of lipoproteins containing apolipoprotein B. Whereas hepatic lipase has been implicated in the clearance and processing of chylomicron remnants in rats, no such defect was found in these mice. We have further characterized the abnormal lipoprotein phenotype in young hepatic lipase-deficient mice and have found more pronounced elevations of high density lipoproteins associated in particular with a 5-fold increase in plasma concentrations of apolipoprotein E. In addition, there was a reduction in the concentration of low density lipoproteins containing apolipoprotein B-100 and B-48 relative to precursor lipoproteins of lower density and a pronounced deficiency of apolipoprotein B-containing low density lipoproteins with density exceeding 1.029 g/mL. Conversion of radiolabeled rabbit intermediate density lipoproteins to low density lipoproteins was reduced by 6-fold as compared with wild-type mice. Although clearance of cholesteryl ester-labeled chylomicrons from the blood was unimpaired in the deficient mice, that of chylomicron remnants was reduced. Furthermore, endocytosis of chylomicron cholesteryl esters into liver cells occurred more rapidly than in wild-type mice. The unimpaired hepatic clearance of injected chylomicron particles in hepatic lipase-deficient mice may be the result of greater acquisition of apoE from high density lipoproteins during remnant formation. These studies thus demonstrate a critical role for mouse hepatic lipase in the formation of small, dense low density lipoproteins, as well as participation in the normal clearance and processing of chylomicron remnants.
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PMID:Metabolism of lipoproteins containing apolipoprotein B in hepatic lipase-deficient mice. 971 27


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