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 effects of amino acid-fortified low casein and fish oil (FO) diets on hyperlipidemia and proteinuria were studied in rats with nephrotoxic serum nephritis. After an antiserum injection, rats were maintained for 14 d on four different experimental diets: a 20% casein diet containing corn oil (CO) or FO, or an 8% casein diet supplemented with cystine plus threonine containing CO or FO. The 8% casein diets reduced urinary protein excretion in nephritic rats without inducing severe growth retardation or fatty liver compared with the basal 20% casein diets. Both the 8% casein diet and the FO diet decreased serum cholesterol, triglyceride and phospholipid levels in nephritic rats, and nonesterified fatty acid levels were decreased by FO feeding. In nephritic animals, hepatic cholesterol synthesis was decreased by the 8% casein diets compared with the 20% casein diets, and tended to be reduced by FO feeding between groups at the same casein levels. No effect of diet was observed on fatty acid synthesis among the nephritic rats. FO administration to the nephritic animals suppressed fecal steroid excretion. While lipoprotein lipase activity was unchanged among the nephritic rats, hepatic triglyceride lipase activity was reduced by either the 8% casein or FO diet. The results suggest that the hypolipidemic action of low casein diets may, at least in part, be due to reduced hepatic cholesterol synthesis and suppressed triglyceride secretion from the liver. They also suggest that the hypolipidemic action of FO may, at least in part, be due to reduced hepatic cholesterol synthesis and decreased fatty acid mobilization from peripheral adipose tissue.
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PMID:Effects of low casein and fish oil on hyperlipidemia and proteinuria in nephritic rats. 786 59

Antihypertensive drugs are expected to have a lipid-lowering effect for use in treating ischemic heart disease. We evaluated the effect of (+)-N-(6-amino-3-pyridil)-N'-[(1S,2R,4R)-bicyclo-[2.2.1]hept-2-yl] -N"- cyanoguanidine hydrochloride (AL0671), a newly synthesized cyanoguanidine-derivative potassium channel opener, on serum lipid and lipoprotein levels in obese Zucker rats, a genetically engineered model of type IV hyperlipidemia. AL0671 dose-dependently decreased systolic blood pressure in obese Zucker rats. Serial administration (for 1 or 2 weeks) of AL0671 (5 mg/kg/day) significantly decreased serum total triglyceride, chylomicron and very-low-density lipoprotein levels with increasing high-density lipoprotein cholesterol, whereas low-density lipoprotein levels did not change. AL0671 (5 mg/kg/day) increased lipoprotein lipase activities 4-fold and hepatic triglyceride lipase activities 3-fold in postheparin plasma. Another urea-derivative compound, AL0674, whose potassium channel-opening activity is diminished, did not affect serum lipid and lipoprotein levels. These results suggested that AL0671 activates both lipoprotein lipase and hepatic triglyceride lipase activities through its potassium channel-opening activity followed by decreasing triglyceride-rich lipoproteins in genetically obese hyperlipemic rats. Therefore, AL0671 might be beneficial in the treatment of hypertensive patients with hypertriglyceridemia (probably with insulin resistance).
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PMID:A possible mechanism of action of a new potassium channel opener, AL0671, on lipid metabolism in obese Zucker rats. 799 82

In 11 patients with IIB hyperlipoproteinemia we studied fasting lipids, lipoproteins, lipoprotein-modifying enzymes, and postprandial lipid metabolism after a standardized oral fat load supplemented with vitamin A before and 12 weeks after treatment with fenofibrate, a third-generation fibric acid derivative. Fasting plasma cholesterol, triglycerides, low-density lipoprotein cholesterol decreased significantly (P < 0.05, P < 0.01, P < 0.01), high-density lipoprotein subfraction 3 cholesterol increased significantly (P < 0.05), and high-density lipoprotein subfraction 2 cholesterol remained unchanged. Postprandial lipemia, i.e., the integrated postprandial triglyceride concentrations corrected for the fasting triglyceride level, and postprandial chylomicron concentrations, as assessed by biosynthetic labeling of chylomicrons with retinyl palmitate, decreased by 40.6% and 60.1% (P < 0.05; P < 0.05), respectively. The activity of lipoprotein lipase (LPL) increased by 33.6% (P < 0.05); the increase in LPL during fenofibrate treatment was positively correlated with the increase in high-density lipoprotein cholesterol (r = 0.84; P < 0.005). Hepatic lipase and cholesteryl ester transfer protein mass and activity remained unchanged. We conclude that lipid-lowering therapy with fenofibrate ameliorates fasting and, more profoundly, postprandial lipoprotein transport in hypertriglyceridemia by curbing postprandial triglyceride and chylomicron accumulation, at least in part, through an increase in LPL activity.
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PMID:Fenofibrate improves postprandial chylomicron clearance in II B hyperlipoproteinemia. 804 77

The pregnancy and delivery of a subject with homozygous familial hypercholesterolemia (FH) and coronary artery disease (CAD) were monitored closely for signs of maternal and fetal distress. Biweekly treatment with low-density lipoprotein (LDL) apheresis using dextran-sulfate cellulose columns was continued throughout the pregnancy, and lipid and lipoprotein levels were evaluated. During the course of the pregnancy and delivery, no signs of maternal coronary insufficiency developed. Serial ultrasonographic measurements of fetal growth indices and the blood flow velocity waveforms (FVWs) of the uterine and umbilical artery did not reveal any sign of fetal growth retardation or insufficiency of the uteroplacental circulation, respectively. During pregnancy, time-averaged concentrations of serum total cholesterol (TC), LDL cholesterol (LDL-C), apolipoprotein (apo) B, and lipoprotein(a) [Lp(a)] showed a gradual decline. Notwithstanding LDL apheresis, a gradual twofold increase of serum triglyceride (TG) levels was found. In the second and third trimester, high-density lipoprotein cholesterol (HDL-C) levels showed a 55% increase that coincided with a 75% reduction in hepatic lipase activity in postheparin plasma, normalizing after parturition. After delivery, lp(a) levels showed an almost twofold increase, which could not be explained by the interruption of LDL apheresis alone, and may be caused by changes in gonadal steroids. Histologic examination of the placenta and the umbilical arteries revealed no atherosclerotic changes, infarctions, or lipid deposits. In general, long-term LDL apheresis in homozygous FH can delay the onset and complications of severe CAD. In case of a pregnancy, LDL apheresis seems feasible and should be continued during the pregnancy to prevent superimposed hyperlipidemia and placental insufficiency.
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PMID:Pregnancy in a patient with homozygous familial hypercholesterolemia treated with long-term low-density lipoprotein apheresis. 808 91

To gain insight into metabolic determinants of high density lipoproteins (HDL) containing apolipoproteins A-I and A-II (LpA-I/A-II) and those containing A-I, but devoid of A-II (LpA-I), the plasma concentration of LpA-I and LpA-I/A-II within the HDL2 and HDL3 density spectrum was measured in 14 normolipidemic male subjects on a standardized diet. Apolipoprotein plasma concentrations of HDL subspecies were compared with the magnitude of postprandial lipemia, activities of lipoprotein lipase and hepatic lipase in postheparin plasma, plasma lecithin:cholesterol acyltransferase (LCAT) activity, and cholesteryl ester transfer protein (CETP) mass. Plasma levels of LpA-I/A-II were 2.5 times higher than levels of LpA-I (123 +/- 20 vs. 48.3 +/- 22.1 mg protein/dl) and the partition of LpA-I and LpA-I/A-II between HDL2 and HDL3 differed in that the proportion of LpA-I associated with HDL2 was greater than that of LpA-I/A-II (23 +/- 19 vs. 6 +/- 6%, P < 0.002). With increasing levels of HDL2, the proportion of LpA-I in HDL2 increased (P < 0.002). Furthermore, levels of LpA-I and LpA-I/A-II were strongly correlated within the HDL2 but not within the HDL3 density region. Plasma levels of LpA-I, but not LpA-I/A-II, were inversely correlated with the magnitude of postprandial lipemia. However, activities of lipoprotein lipase and hepatic lipase tended to show stronger associations with the partition of LpA-I/A-II between HDL2 and HDL3 than with that of LpA-I. Within the HDL3, but not the HDL2 density spectrum, LpA-I/A-II exhibited a positive association with plasma LCAT activity, while LpA-I displayed an inverse association with plasma CETP mass. These results are consistent with differences in substrate properties of LpA-I and LpA-I/A-II for lipoprotein modifying enzymes and imply different, but overlapping metabolic pathways of LpA-I and LpA-I/A-II.
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PMID:High density lipoproteins with differing apolipoproteins: relationships to postprandial lipemia, cholesteryl ester transfer protein, and activities of lipoprotein lipase, hepatic lipase, and lecithin: cholesterol acyltransferase. 816 33

The aetiology of familial combined hyperlipidaemia remains obscure, with both genetic and environmental factors contributing to the phenotype, which is frequently associated with premature coronary heart disease. We have studied lipoprotein lipase (LPL) activity and hepatic lipase (HL) activity in patients with coronary heart disease to determine whether variation in lipase activities contributes to this phenotype. Forty-one patients (mean age 50 years; 30 male) were selected on the basis of cholesterol levels above 6.5 mmol/l and triglyceride levels above 2.2 mmol/l, with apoprotein B values over the 90th percentile. There was a family history of premature coronary heart disease in 78% and a personal history in 64%, at mean age 44, the patient group therefore predominantly corresponded to the common definition of familial combined hyperlipidaemia, appropriate in the absence of molecular markers. None of the patients was diabetic; hypertension and smoking were not over represented. Blood samples were taken following intravenous administration of heparin (100 IU/kg body wt), and LPL and HL activities were measured. Mean post-heparin LPL was significantly lower in patients than controls 10 min after heparin administration (2.98 +/- 1.04 and 3.86 +/- 0.93 mumol ml-1 h-1, respectively, P = 0.001), and 37% patients had values below the 10th percentile of controls. Both male and female patients had significantly higher HL activities than their respective controls at 5, 10, 20 and 30 minutes post-heparin. As expected, both female patients and controls had lower HL activities than males, although this sex difference did not reach statistical significance in the patient group.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein lipase activity in patients with combined hyperlipidaemia. 818 54

The effect of the sulfur-substituted fatty acid analogue 1,10 bis(carboxymethylthio)decane, also known as 3-thiadicarboxylic acid, on puromycin aminonucleoside-induced nephrotic hyperlipidemia was studied in rats. Treatment with 3-thiadicarboxylic acid (250 mg/kg) for 5 days reduced plasma levels of triglycerides from 5.8 to 2.7 mmol/L and cholesterol from 11.0 to 7.7 mmol/L. This was accounted for by decreases in very-low-density lipoprotein triglycerides, very-low-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, without any major changes in the composition of plasma lipoproteins. The activities of two enzymes involved in fatty acid synthesis (ATP:citrate lyase and fatty acid synthetase) were inhibited by 3-thiadicarboxylic acid treatment, whereas acetyl-coenzyme A carboxylase activity was unchanged. In contrast, treatment with the sulfur-substituted fatty acid analogue induced the peroxisomal beta-oxidation of fatty acids ninefold and the mitochondrial beta-oxidation by 54% to 73%, depending on the substrate used. This was accompanied by a 26% reduction in hepatic triglyceride secretion rate. The hepatic phosphatidate phosphohydrolase activity was unchanged. 3-Thiadicarboxylic acid treatment suppressed the activity of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase, by 58%, whereas hepatic LDL receptor expression was unaltered. The activities of lipoprotein lipase and hepatic lipase were unchanged by treatment. These results demonstrated that treatment with 3-thiadicarboxylic acid ameliorates hyperlipidemia in experimental nephrosis primarily by decreasing the overproduction of very-low-density lipoprotein present. The data also indicate that hepatic very-low-density lipoprotein synthesis and secretion is strongly influenced by the availability of the fatty acid substrate under the same hyperlipidemic conditions.
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PMID:Effect of 3-thiadicarboxylic acid on lipid metabolism in experimental nephrosis. 821 98

Hyperlipidemia is prominent among the disturbances in intermediary metabolism that occur subsequent to infections by microorganisms. The response to such infections is known to involve several cell types and is mediated by cytokines. We hypothesized that metabolic lipid disturbances seen during infection in cystic fibrosis (CF) patients may partly be the result of excessive tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine known to cause a large spectrum of pathophysiologic alterations, including impaired lipid metabolism. Therefore, we determined the circulating concentration of TNF-alpha and analyzed its relationship to lipid and lipoprotein levels, as well as lipoprotein lipase activity, in 31 CF patients. Plasma TNF-alpha values were significantly (p < 0.01) elevated in patients with CF compared with controls. The CF subjects were found to have decreased plasma cholesterol (25%), LDL cholesterol (35%), and HDL cholesterol (19%) concentrations, whereas plasma triglycerides were significantly increased (p < 0.001). The apo A-I level was reduced (p < 0.005), whereas apo B levels were normal. Low levels of the major essential fatty acids were found in the plasma of the CF patients, and the triene/tetraene ratio confirmed their essential fatty acid deficiency. Postheparin lipolytic activity was lower in CF patients than in controls, and the decreased activity was accounted for primarily by a decline in hepatic lipase. A significant positive correlation (p < 0.001, r = 0.70) was found between TNF-alpha and plasma triglyceride levels. However, no association was noted between TNF-alpha and essential fatty acid, cholesterol, or lipoprotein cholesterol levels, or with lipoprotein lipase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Circulating tumor necrosis factor-alpha levels and lipid abnormalities in patients with cystic fibrosis. 823 19

Eleven men with hypoalphalipoproteinemia (HPAL; fasting plasma high density lipoprotein (HDL) cholesterol level of < 0.9 mmol/l), mild hypertriglyceridemia (HTG; triglycerides (TG) level of 1.75-7.5 mmol/l) and a normal calculated LDL cholesterol level (< 3.7 mmol/l) participated in a randomized, double-blind, double-placebo, crossover trial to compare the effect of two drugs, lovastatin (40 mg once daily) and gemfibrozil (600 mg twice daily), on clearance of postprandial lipoproteins. A 2-week washout period separated drug treatment periods of 6 weeks each. Ten subjects completed each treatment period. After ingestion of a vitamin A fat load, plasma, chylomicron and non-chylomicron retinyl palmitate (RP) and TG responses (areas under curves) were reduced in all subjects on gemfibrozil therapy and in 7 on lovastatin therapy. There was close correlation between change in fasting TG (but not fasting HDL-cholesterol) and change in postprandial RP areas on gemfibrozil but not lovastatin therapy. Postheparin lipoprotein lipase (LPL) and hepatic lipase (HL) activities were increased by gemfibrozil therapy while only a mild elevation in LPL activity alone was seen on lovastatin therapy. These data indicate that improvement in HTG is the main feature associated with improvement in postprandial lipemia and this is likely due to LPL-mediated enhancement of lipolytic hydrolysis. Gemfibrozil is more effective than lovastatin in attenuating postprandial lipemia in the HPAL/HTG syndrome.
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PMID:Effect of gemfibrozil and lovastatin on postprandial lipoprotein clearance in the hypoalphalipoproteinemia and hypertriglyceridemia syndrome. 831 63

It is unknown whether the clearance of atherogenic chylomicron remnants and the postprandial lipoprotein metabolism in general can be improved by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors in subjects with familial combined hyperlipidemia (FCH). Therefore, the postprandial chylomicron remnant clearance was studied in nine normolipidemic untreated controls and seven FCH patients before and after treatment with simvastatin using an oral vitamin A-fat load (24 hours, 50 g/m2). Treatment with simvastatin reduced plasma cholesterol level by 16% (mean +/- SEM, 8.1 +/- 0.8 v 6.8 +/- 0.8 mmol/L; P < .05) and plasma apolipoprotein (apo) B level by 19% (1.6 +/- 0.2 v 1.3 +/- 0.2 g/L; P < .05). Plasma apo E level (89.6 +/- 21.0 mg/L) was reduced by 29% (63.5 +/- 14.1 mg/L; P < .05). High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) levels did not change; consequently, the reductions seen had been due to a decrease in very-low-density lipoprotein (VLDL) levels. Fasting plasma triglyceride (30% reduction) and plasma apo C-II (31% reduction) levels did not change significantly. Mean postheparin plasma lipoprotein lipase (LPL) activity increased by 13% after treatment (90.4 +/- 19.8 v 102.6 +/- 20.3 mU/mL; P < .05), but hepatic lipase (HL) activity was not altered. The clearance of chylomicrons (Sf > 1,000), expressed as the area under the 24-hour retinyl palmitate curve, did not change with simvastatin (52.8 +/- 12.9 v 51.8 +/- 13.4 h.mg-1/L).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Simvastatin improves chylomicron remnant removal in familial combined hyperlipidemia without changing chylomicron conversion. 848 74


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