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)

Transient lowering of blood levels of free fatty acids (FFA) in man and experimental animals after ingestion of fat has been noted by many investigators and has been attributed to inhibition of mobilization of fatty acids from adipose tissue. Studies on lipid mobilizing activity in in vitro systems containing glucagon, insulin and anti-insulin anti-bodies as factors modifying lipolysis indicate that insulin is the basic inhibitor of lipolysis in the blood in the period immediately following feeding of animals. This observation has been confirmed by direct determinations of insulin levels by the radioimmunologic method. Experiments in which substances influencing activity of the autonomic nervous system were used show that ingestion of fats stimulates insulin secretion as a result of cholinergic stimulation. Studies on lipolytic activity of blood serum confirmed an essential role of lipoprotein lipase in the mechanism of deposition of triglycerides in adipose tissue during alimentary lipemia. The role of prostaglandins and intestinal hormones (enteroinsular axis) in the mechanism of regulation of FFA levels during alimentary lipemia is also discussed.
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PMID:Factors regulating blood levels of free fatty acids during alimentary lipemia. 118 13

10 to 20% of [1-14C] palmitate injected into pregnant guinea pigs was recovered in lipids of their fetuses. From these data and the rate of transport of palmitate in maternal blood, it appears that placental transport of free fatty acids can account for the accumulation of lipids in late gestational fetuses. About 80% of the labeled palmitate in the fetus appeared initially in lipids of the liver. 14C appeared in plasma triglyceride fatty acids after a few minutes and subsequently accumulated in lipids of white and brown adipose tissue, suggesting that much of the palmitate deposited in adipose tissue were derived from hepatogenous triglyceride fatty acids. By contrast, 14C was usually maximal in heart and carcass lipids before it appeared in plasma triglyceride fatty acids. Lipoprotein lipase activity in fetal adipose tissue was low, and activity of cofactor protein of lipoprotein lipase in fetal blood plasma was much lower than that observed in other mammalian species. On the basis of these and earlier observations, it is concluded that the accumulation of triglycerides in liver and blood plasma of fetal guinea pigs during late gestation is at least partly the result of the large uptake of maternally derived free fatty acids by the fetal liver accompanied by rapid synthesis and secretion of triglyceride-rich very low density lipoproteins into the blood. However, limited uptake of triglyceride fatty acids in adipose tissue may contribute to the fatty liver and hyperlipemia.
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PMID:Genesis of fatty liver and hyperlipemia in the fetal guinea pig. 119 88

Hyperlipidemia is one of the major risk factors for cardiovascular death in long-term hemodialysis (HD) patients. To clarify whether unfractionated heparin (UFH) contributes to the pathogenesis of hyperlipidemia, nine Type IIb, seven Type IV, and 10 normolipidemic patients, who had been dialyzed with 80.7 IU/Kg heparin, were dialyzed with 40 anti-Xa U/kg of low molecular weight heparin (LMWH) (Logiparin, Novo-Nordisk, Gentfe, Denmark) for 6 months. Seven normolipidemic patients were also dialyzed with heparin as controls. Decreases in triglyceride (TG) during HD with LMWH were significantly less than those with heparin. However, lipoprotein lipase activities (LPL) during HD with LMWH and heparin, and those before and after 6 months on LMWH, were no different. During the 6 months on LMWH, serum total cholesterol, TG, and alpha lipoprotein significantly decreased in Type IIb patients but did not change in Type IV. In contrast, beta lipoprotein slightly increased in Types IIb, IV, and normolipidemic patients who were dialyzed with LMWH but was unchanged in the controls. These observations suggest that UFH aggravates hyperlipidemia in patients, but these effects cannot be attributed to depletion of endothelial LPL liberated by UFH.
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PMID:Long-term use of low molecular weight heparin ameliorates hyperlipidemia in patients on hemodialysis. 133 45

A previous study reported that heterozygotes for lipoprotein lipase (LPL) deficiency have reduced LPL, the lipoprotein pattern classified as familial combined hyperlipidemia (FCHL), elevated apolipoprotein (apo) B levels, and reduced high density lipoprotein (HDL) levels. These findings suggest that subjects with reduced LPL may form one subset of the FCHL population. The purpose of the present study is to determine whether a subset of patients with FCHL have reduced LPL. Three patient populations with FCHL were studied: 1) subjects with the diagnosis of FCHL (n = 9) established by previous family studies, 2) clinic patients with a tentative diagnosis of FCHL (n = 14), and 3) subjects undergoing angiography who had coronary artery disease (CAD) and a diagnosis of FCHL by family study (n = 33). Two of nine subjects with the established diagnosis of FCHL, five of the 14 FCHL clinic patients, and 13 of the 33 CAD subjects with FCHL had reduced LPL activity in the same range as do individuals who are obligate heterozygotes for LPL deficiency. Subjects with FCHL and reduced LPL had higher plasma triglyceride (p < 0.01) and lower HDL cholesterol (p < 0.025) levels than did the subjects with FCHL and normal LPL levels (327 +/- 201 versus 210 +/- 122 mg/dl [mean +/- SD] and 36 +/- 7 versus 44 +/- 13 mg/dl, respectively). Thus, in all three groups of patients with apparent FCHL, 20 of 56 subjects (36%) had reduced LPL, suggesting that one subset of the FCHL population may be identified by an abnormality in LPL activity that is associated with lipoprotein abnormalities.
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PMID:Familial combined hyperlipidemia and abnormal lipoprotein lipase. 139 May 89

Hypoalphalipoproteinemia (HPAL) with mild hypertriglyceridemia (HTG) is associated with increased coronary artery disease (CAD) risk. The aim of this study was to examine the metabolism of postprandial lipoproteins in HPAL/HTG subjects (n = 21). They had a fasting plasma high density lipoprotein (HDL) cholesterol level < 0.9 mmol/l, a triglycerides (TG) level of 2.0-7.1 mmol/l, and a normal low density lipoprotein (LDL) cholesterol level (< 3.7 mmol/l). They were either homozygous for apoprotein E3 (n = 13) or heterozygous for apoprotein E4 (n = 5) or E2 (n = 3). After ingestion of a vitamin A fat load, plasma and chylomicron (CM) retinyl palmitate (RP) response (areas under curves) was three times and non-CM RP response 2.5 times greater than in normolipidemic control subjects (n = 13). There was close correlation between fasting plasma TG level and postprandial RP response in HPAL/HTG subjects (plasma, r = 0.87; CM, r = 0.89; and non-CM, r = 0.84). In control subjects this correlation was present for plasma RP (r = 0.80) and CM RP (r = 0.61) but not for non-CM RP (r = 0.53). In contrast, postprandial RP response was not correlated with fasting plasma HDL cholesterol levels for both groups. There was also no correlation between fasting TG and fasting HDL cholesterol. Postheparin lipoprotein lipase and hepatic lipase activities were slightly higher in HPAL/HTG subjects. The pattern of postprandial change in HDL composition was similar to that in control subjects. These data indicate enhanced postprandial lipemia in the HPAL/HTG syndrome, and this may account for their increased CAD risk.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Delayed clearance of postprandial chylomicrons and their remnants in the hypoalphalipoproteinemia and mild hypertriglyceridemia syndrome. 139 May 90

The metabolic origins of equine hyperlipaemia were investigated by analysing the concentration and composition of plasma lipoproteins in 18 ponies with the condition. The mean concentrations of cholesterol, triglyceride and very low density lipoproteins (VLDL) were increased by 4-, 52- and 19-fold, respectively, compared with a control group of 18 healthy ponies. These increases were due to the appearance of a buoyant VLDL fraction (VLDL1) not present in healthy ponies. The mean diameter of VLDL1 particles was 44% greater than control VLDL, and the particles were enriched in triglyceride and free cholesterol and depleted of cholesteryl esters, phospholipid and protein. The apolipoprotein (apo) B-100 content of VLDL1 was reduced and the ratio of apoB-100 to apoB-48 particles was 1:1, compared with 2:1 in control VLDL. The VLDL1 was also enriched in apoE, but had normal complements of apoC-II and apoC-III. The conventional VLDL (called VLDL2), LDL and HDL fractions were moderately enriched with triglyceride, and HDL contained increased amounts of apoE, apoC-II and apoC-III. The activities of lipoprotein lipase and hepatic lipase, the enzymes responsible for the catabolism of VLDL and their remnants, were increased by 2- and 3-fold, respectively, in response to the increased concentrations of their substrates. The composition of VLDL1 suggested that the liver was maximising the secretion of triglyceride by producing larger number of VLDL particles that accommodated a greater mass of triglyceride by having apoB-48 rather than apoB-100 as their structural protein. Plasma free fatty acid (FFA) concentrations were elevated in 17 of the 18 ponies, suggesting that increased FFA flux might be the stimulus for hepatic triglyceride synthesis and VLDL secretion. We conclude that overproduction, rather than defective catabolism, of VLDL was the cause of the hyperlipidaemia and that lipid lowering agents which reduce VLDL synthesis, by decreasing adipose lipolysis and FFA flux, are candidates for the management of hyperlipaemia.
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PMID:Plasma lipids, lipoproteins and post-heparin lipases in ponies with hyperlipaemia. 139 7

Correction of cardiovascular risk factors is of particular significance in a high-risk population, such as that of diabetic patients. This paper reports the effects of one-month administration of 400 mg/day Bezafibrate (BZF), followed by a two-month wash-out and one-month administration of 500 mg/day Acipimox (APX) or vice versa in a random order in 16 Type 2 diabetic patients with diet-resistant hyperlipidaemia and in good metabolic control (HbA1c less than 8%), on plasma fibrinogen and on their lipid pattern. Metabolic control displayed a nonsignificant improvement (HbA1c) during both treatments (stable body weight). Both BZF and APX produced a 14% decrease in total CHOL (p less than 0.01), whereas BZF was more effective in reducing triglycerides (tg) (-37% vs -15%). The marked BZF-induced Tg reduction was associated with a proportional decrease in Apo B, while an increase in total HDL-, HDL2 and HDL3-CHOL, together with a significant increase in Apo AI, was observed. APX treatment resulted in a HDL2-CHOL increase only (+29%). Both drugs reduced VLDL-CHOL (BZF -37%; APX -15%) and VLDL-Tg (-56% and -34%). In BZF treated patients Apo CIII fell indicating a possible reduction of specific inhibition of lipoprotein lipase activity, while APX affected both Apo CII (+23%) and Apo CIII (-26%) and led to a 62% Apo CII/CIII ratio increase. BZF alone led to a significant 25% decrease in plasma fibrinogen (from 415 +/- 14.3 to 312.1 +/- 18.1 SEM mg/dl, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of the effects of bezafibrate and acipimox on the lipid pattern and plasma fibrinogen in hyperlipidaemic type 2 (non-insulin-dependent) diabetic patients. 139 77

An increased risk of developing premature atherosclerosis is associated with stress, diabetes, obesity, and hypertension. These conditions are associated with insulin resistance, hyperglycemia, hypertriglyceridemia and hypercholesterolemia. An alternative way of interpreting insulin resistance is to consider that metabolism in this condition would be regulated to a greater extent by stress hormones and in particular by cortisol. Glucocorticoids and fatty acids (which are produced in response to stress) antagonise the actions of insulin in promoting glucose uptake and protein synthesis, in decreasing gluconeogenesis and protein catabolism, and promoting the clearance of intermediate density lipoprotein and low density lipoprotein from the circulation by the liver. They also promote the secretion of very low density lipoprotein thus producing hypertriglyceridemia and hypercholesterolemia. By contrast to this antagonism, cortisol can also facilitate the action of insulin in stimulating the storage of energy via glycogen and fatty acid synthesis and through lipoprotein lipase in adipose tissue. These effects are significant in relation to obesity and to weight gain. An increased control of metabolism by cortisol therefore produces changes in metabolism that are potentially atherogenic and it is associated with insulin resistance and the other risk factors for atherosclerosis. Benfluorex treatment improves insulin sensitivity and has antihyperglycemic and hypolipidemic effects in human beings and in experimental animals. These effects can be observed independently of weight loss, but lowering food intake also produces a metabolic benefit. Long-term treatment with benfluorex can also decrease stress responses in terms of glucocorticoid release and the stimulation of lipolysis probably by its serotoninergic control of the hypothalamic-pituitary-adrenal axis. Such an action provides for an integrated treatment of the obese-diabetic-hyperlipidemic syndrome. Benfluorex produces overall changes in metabolism that tend to normalise the major risk factors associated with premature atherosclerosis. This provides a potential advantage over other therapies for atherosclerosis which may ameliorate a symptom (e.g., hyperlipidemia) without treating the underlying metabolic disturbance that predisposes to atherogenesis.
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PMID:[Mode of action of benfluorex. Recent data]. 143 2

Post-prandial lipaemia was investigated in a group of nine subjects with nephrotic syndrome by following the concentrations of triglyceride and retinyl palmitate in the d < 1.006 g ml-1 fraction of plasma after a standard oral fat load containing vitamin A. Lipoprotein lipase and hepatic triglyceride lipase activities were measured in post-heparin plasma. Subjects with other renal disease but insignificant proteinuria acted as controls. The time course of the lipaemic response was similar in both groups although individual patients demonstrated a prolonged lipaemia. Overall, there were no significant differences in the rise in triglyceride at 6 h (nephrotic--median 2.53 mmol l-1; range 0.87-4.76 vs. control 1.88; 0.38-4.12, P = 0.34), the peak concentration of retinyl palmitate (nephrotic 0.87 mg dl-1; 0.27-2.16 vs. control 0.65; 0.24-1.89, P = 0.97) or the areas under the curve from 0-24 h for triglyceride (nephrotic 10.5 mmol. h l-1; 2.9-43.6 vs. control 9.7; 4.3-27.0, P = 1.0) or retinyl palmitate (5.5 mg.h dl-1; 1.0-23.4 vs. 4.3; 1.5-12.4, P = 0.7). At baseline, the particles in the d < 1.006 g ml-1 fraction of plasma from nephrotic subjects had a higher free cholesterol:phospholipid ratio but this difference was no longer apparent 6 h after the test meal. There were no differences in total heparin-releasable lipase, lipoprotein lipase or hepatic triglyceride lipase activities between the two groups. These data suggest that impaired clearance of chylomicrons is not a major contributor to nephrotic hyperlipidaemia in man.
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PMID:Post-prandial lipoprotein metabolism in nephrotic syndrome. 147 53

Data from several different studies are reviewed suggesting that a subset of hypertension is associated with metabolic abnormalities involving lipids, insulin, and often obesity, all aggregating strongly in families. Persons with 'familial dyslipidaemic hypertension (FDH)' have an especially high risk of early coronary disease. The clinical and biochemical features of FDH are compared with Reaven's Syndrome X, familial combined hyperlipidaemia, dense LDL subfractions, diabetes, impaired glucose tolerance, central and general obesity, pre-diabetes, pre-hypertension, and heterozygous lipoprotein lipase deficiency. Some contribution from major gene effects is suggested in specific subsets reported in several different genetic studies reviewed in this report. It seems likely that multiple metabolic abnormalities are genetically heterogeneous. The data also suggest significant contributions from environmental factors such as diet and physical activity.
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PMID:Familial dyslipidaemic hypertension and other multiple metabolic syndromes. 148 41


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