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)

We report an impressive decline in plasma lipid resistance to oxidation during Triton-WR-1339-induced hyperlipidemia in rats. This decline is associated with a modification in the balances between alpha-tocopherol and lipids and alpha-tocopherol and ascorbate. These results are consistent with a weak resistance of accumulated native lipoproteins in plasma to oxidation, during a 6-hour time course, and they suggest a misunderstood role of lipoprotein catabolic enzymes: to improve this characteristic. Conclusively, the results lead us to propound Triton-induced hyperlipidemia as an original model for studying the balance impairment between antioxidants and oxidizable substrates.
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PMID:Weak resistance to oxidation of native lipoproteins in Wistar rats. 851 35

The hypolipidemic effect of Senegae Radix, i.e. "Senega," was investigated in normal and hyperlipidemic mice. The n-butanol fraction of the methanol extract of Senegae Radix (SN) (5 mg/kg) significantly reduced the blood triglyceride level of normal mice 7 h after intraperitoneal administration (p < 0.05) and also significantly reduced the blood triglyceride level of cholesterol-fed mice under similar conditions (p < 0.05). SN (5 mg/kg) also reduced the blood triglyceride and cholesterol levels after repeated administration to cholesterol-fed mice. SN also decreased the blood triglyceride level in Triton-induced hyperlipidemia. It is suggested that this fraction contains one or more hypolipidemic components including the main triterpenoid glycoside, senegin-II, which significantly reduces the levels of blood triglycerides in normal mice.
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PMID:Intraperitoneal administration of Senegae Radix extract and its main component, senegin-II, affects lipid metabolism in normal and hyperlipidemic mice. 885 Mar 32

The effect of dietary fiber on the pattern of postprandial lipemia was examined in two studies with male Wistar rats. In the first study, groups of rats were killed after food deprivation (0 h) or 1, 4.5 or 8.5 h after a high fat test meal containing either cellulose (CL) or oat bran (OB). Plasma triglycerides (TG) were higher in the OB group at 4.5 h compared with both the 0-h and the CL-groups at 4. 5 h. In both groups, LDL and TG-rich lipoprotein cholesterol (TRL-C) concentrations were higher at 8.5 h than at 0 h; HDL cholesterol was significantly lower at 8.5 h than at 0 h for the OB group only. The enhanced lipemia when OB was fed may stimulate cholesterol movement from HDL to LDL and TRL. To examine whether TRL secretion rates were responsible for the enhanced lipemia, a second study was conducted. Rats were fitted with jugular catheters and allowed to recover. Two groups were fed either CL or OB and infused with Triton-1339 (400 mg/kg). Two control groups were not fed and were infused with either Triton or saline. Rats were killed 2.5 h after infusion. Plasma TG was 10-fold higher in the Triton group than in the saline group, but did not differ between the OB and CL groups. The relative contribution of TRL-C to total cholesterol was significantly greater in the Triton control than in the OB and CL groups. Enhanced secretion of TRL was not responsible for the lipemia observed in the first study. Rather, alterations in clearance rate were responsible.
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PMID:Alimentary lipemia is enhanced in fiber-fed rats. 961 65

Moderate protein restriction throughout pregnancy in the rat leads to relative hyperlipidaemia and blunted insulin responsiveness of lipid fuel supply, and impairs foetal growth. The present study examined the basis for these changes. Isocaloric 8% (vs 20%) protein diets were provided throughout pregnancy. Rats were sampled at 19-20 days of gestation. Protein restriction enhanced triacylglycerol (TAG) secretion rates (estimated using Triton WR 1339) 1.6-fold (P < 0.05) in the post-absorptive state. Insulin infusion (4.2 mU/kg per min) decreased plasma TAG concentrations by 33% (P < 0.05) and 48% (P < 0.05) in control (C) and protein-restricted (PR) pregnant groups, an effect associated with suppression of TAG secretion by 42% (P < 0.05) and 51% (P < 0.01) respectively, in the C and PR groups. Since TAG concentrations decline more rapidly, while TAG secretion is enhanced, TAG utilisation during hyperinsulinaemia is enhanced in the PR group. We evaluated whether these changes were associated with dysregulation of lipolysis using adipocytes from two abdominal depots (mesenteric and parametrial). Noradrenaline-stimulated glycerol release was enhanced in parametrial adipocytes (by 40%; P < 0.05) from PR pregnant rats. The anti-lipolytic action of insulin at low concentrations (< or = 15 microU/ml) was impaired by protein restriction (adipocytes from both depots). There was no evidence for altered intra-hepatic regulation of fatty acid (FA) disposal at the level of carnitine palmitoyltransferase. Our results demonstrate increased post-absorptive production of non-carbohydrate energy substrates (TAG and FA) as a consequence of mild protein restriction during pregnancy. These adaptations contribute to a homeostatic strategy to reduce the maternal requirement for gluconeogenesis from available amino acids, optimising the foetal protein supply. Protein restriction also enhances TAG turnover during hyperinsulinaemia. This effect is not a consequence of abnormal regulation of hepatic lipid metabolism by insulin.
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PMID:Moderate protein restriction during pregnancy modifies the regulation of triacylglycerol turnover and leads to dysregulation of insulin's anti-lipolytic action. 978 99

The effects of ip administration of NSAIDs in experimentally induced hyperlipidemia in rats was studied. An isotonic solution of Triton WR1339 (tyloxapol) was administered ip to rats one hour after ip administration of the examined anti-inflammatory drug. After 24 h, blood was collected for the determination of plasma total cholesterol (TC), LDL and trigluceride (TG) concentrations. The NSAIDs used in our experimental model are selective or non selective COX-1 inhibitors as well as one non selective COX-2 inhibitor. Most of the drugs significantly reduced the TC, TG and LDL concentrations in the plasma of hyperlipidemic rats. While studies link atheromatosis to inflammation, our results potentially also link anti-inflammatory activity with hypolipidemia. Thus, NSAIDs not only may address the inflammatory aspect of atherosclerosis but also may contribute directly by inducing hypolipidemia.
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PMID:Experimental hyperlipidemia and the effect of NSAIDs. 1223 Dec 15

Triton WR-1339, a non-ionic detergent, added to canine serum or to ultracentrifugally separated lipoproteins, induced changes in the lipoproteins which were dependent upon concentration of detergent and class of lipoproteins. D 1.063 to 1.21 lipoprotein (alpha-LP) was especially sensitive to the action of triton. Addition of 2 mg. of triton to 1 mg. of alpha-LP (based on protein content), induced only slight changes in the electrophoretic and flotation characteristics of the lipoprotein. With a tenfold increase of the detergent (triton:alpha-LP, 20:1), the mixture, analyzed by starch gel and paper electrophoresis, yielded a tritonlipid complex which remained close to the origin, and a nearly lipid-free protein with electrophoretic mobility higher (starch gel) or lower (paper) than native alpha-LP. The splitting of the lipid and protein moieties of alpha-LP could not be clearly shown when the same mixture was analyzed by free boundary electrophoresis. Triton alone moved only slightly in an electrical field (paper, starch gel, Tiselius); it sedimented during ultracentrifugation at D 1.006 and D 1.063 and floated at D 1.21. D 1.006 to 1.063 lipoproteins (beta-LP), required larger amounts of triton to show changes. These were evident in 40 to 80:1 mixtures of triton and beta-LP. In starch gel and paper electrophoresis triton retained, in a position close to the origin, part of the lipids of beta-LP; the remaining beta-LP fraction, impoverished of lipids, had electrophoretic mobility similar to native beta-LP. The triton-lipid complex sedimented at D 1.063. After addition of triton to complexes [chylomicron-alpha-P-I(131)] or [lipomul-alpha-LP-1(131)], the electrophoretic and ultracentrifugal analyses of these mixtures revealed that the labeled protein was removed from the triglyceride component. Triton also prevented the occurrence of the interaction between lipomul and alpha-LP and the hydrolysis of both chylomicrons and lipomul-alpha-LP by lipoprotein lipase. It is postulated that, if the changes in lipoproteins and chylomicrons observed in vitro occur in vivo, they could account, at least in part, for the hyperlipemia which develops in animals following administration of triton.
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PMID:Triton hyperlipemia in dogs. I. In vitro effects of the detergent on serum lipoproteins and chylomcrons. 1374 54

A study was made of the relationship of blood lipids to the development of experimental atherosclerosis. Rabbits fed a diet containing cholesterol were found to develop hyperlipemia characterized by a great increase in blood cholesterol and a much lesser increase in blood phospholipids; after several weeks they manifested conspicuous atherosclerosis of the aorta, as has often been observed by others. Comparable rabbits fed the same diets containing added cholesterol were given in addition repeated intravenous injections of the surface-active agents Tween 80 and Triton A20; these animals developed hyperlipemia which was characterized by a great increase in blood cholesterol and an equivalent or even greater increase in phospholipids, and they had much less atherosclerosis than did the control rabbits fed cholesterol alone. In further experiments it was observed that repeated intravenous injections of Tween 80 did not result in resorption of previously induced atherosclerosis in rabbits. The findings are discussed in relation to the pathogenesis of natural and experimental atherosclerosis.
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PMID:The influence of intravenously administered surface-active agents on the development of experimental atherosclerosis in rabbits. 1482 10

LDL receptor-deficient (LDLR(-/-)) mice fed a Western diet exhibit severe hyperlipidemia and develop significant atherosclerosis. Apolipoprotein E (apoE) is a multifunctional protein synthesized by hepatocytes and macrophages. We sought to determine effect of macrophage apoE deficiency on severe hyperlipidemia and atherosclerosis. Female LDLR(-/-) mice were lethally irradiated and reconstituted with bone marrow from either apoE(-/-) or apoE(+/+) mice. Four weeks after transplantation, recipient mice were fed a Western diet for 8 weeks. Reconstitution of LDLR(-/-) mice with apoE(-/-) bone marrow resulted in a slight reduction in plasma apoE levels and a dramatic reduction in accumulation of apoE and apoB in the aortic wall. Plasma lipid levels were unaffected when mice had mild hyperlipidemia on a chow diet, whereas IDL/LDL cholesterol levels were significantly reduced when mice developed severe hyperlipidemia on the Western diet. The hepatic VLDL production rate of mice on the Western diet was decreased by 46% as determined by injection of Triton WR1339 to block VLDL clearance. Atherosclerotic lesions in the proximal aorta were significantly reduced, partially due to reduction in plasma total cholesterol levels (r=0.56; P<0.0001). Thus, macrophage apoE-deficiency alleviates severe hyperlipidemia by slowing hepatic VLDL production and consequently reduces atherosclerosis in LDLR(-/-) mice.
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PMID:Effect of macrophage-derived apolipoprotein E on hyperlipidemia and atherosclerosis of LDLR-deficient mice. 1504 72

Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.
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PMID:Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats. 1618 30

Animals of various species are widely used as models with which to study atherosclerosis and the lipoprotein metabolism. The objective of this study was to investigate the lipoprotein profiles in Wistar rats and New Zealand white rabbits with experimentally induced hyperlipidemia by means of ultracentrifugation. The Schlieren curves were utilized to compare suckling and adult rat sera to determine whether aging causes alterations in lipoprotein profiles. A striking feature of the data is the high concentration of low-density lipoproteins (LDL), (>5.2 mmol/l cholesterol) in the 2-week old rat serum pool which was greatly decreased in the 3-weeks rat serum pool (<1.3 mmol/l cholesterol). Additional experiments were performed to permit a direct comparison of the amounts of lipoprotein present in rat sera in experimental hyperlipidemia post-Triton WR 1339 administration. Rapid changes in concentrations in very low-density lipoproteins (VLDL), LDL and high-density lipoproteins (HDL) were observed after Triton injection. The administration of Triton WR 1339 to fasted rats resulted in an elevation of serum cholesterol levels. Triton physically alters VLDL, rendering them refractive to the action of lipolytic enzymes in the blood and tissues, preventing or delaying their removal from the blood. Whereas the VLDL concentration was increased markedly, those of LDL and HDL were decreased at 20 h after Triton treatment. Rabbits were fed a diet containing 2% cholesterol for 60 days to develop hyperlipidemia and atheromatous aortic plaques. A combination of preparative and analytical ultracentrifugation was used to investigate of LDL aliquots, to prepare radioactive-labeled lipoproteins and to study induced hyperlipidemia in rabbits. Analytical ultracentrifugation was applied to investigate the LDL flotation peaks before and after cholesterol feeding of rabbits. Modified forms of LDL were detected in the plasma of rabbits with experimentally induced atherosclerosis. ApoB-containing particles, migrating as LDL, intermediate density lipoproteins and VLDL were the most abundant lipoproteins. Gamma camera in vivo scintigraphy on rabbits with radiolabeled lipoproteins revealed visible signals corresponding to atherosclerotic plaques of the aorta and carotid arteries.
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PMID:Evaluation of rat and rabbit sera lipoproteins in experimentally induced hyperlipidemia by analytical ultracentrifugation. 1630 70


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