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)

Fibroblasts from 12 normotriglyceridemic subjects and 30 hypertriglyceridemic patients and family members were used to investigate triglyceride synthesis and the influence of triiodothyronine on it. The monolayers were incubated for 72 hours with and without the thyroid hormone, followed by incorporation studies of radiolabeled acetic acid or palmitic acid into the cellular triglyceride fraction. Triiodothyronine had no influence on triglyceride synthesis of normal cell lines and of cells derived from patients with secondary hypertriglyceridemia, whereas fibroblasts from endogenous type IV patients showed higher rates of triglyceride synthesis under identical conditions. Values for type IV were in the range of 134% to 466% of the hormone-free control incubations. In cultures derived from patients with familial combined hyperlipidemia, no stimulation by triiodothyronine was observed: values were in the range of 64% to 144% of the hormone-free controls. Three out of four lines with type V gave "normal" values and are supposed to represent secondary hypertriglyceridemia, whereas one line may express endogenous type IV. The evidence obtained in vitro with cultured cells indicates different metabolic defects in endogenous type IV and familial combined hyperlipidemia; it also shows the biochemically heterogenous nature of the disease "hypertriglyceridemia."
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PMID:Effect of triiodothyronine on triglyceride synthesis in human fibroblasts in different types of hypertriglyceridemia. 229 72

To explore the possible association of hyperlipidemia with hyperammonemia and aspirin ingestion, the effects of NH4+, salicylate, and carnitine on the oxidation of [1-14C]palmitic acid to acid-soluble products (ASP) and to CO2 were investigated in rat liver slices. DL-carnitine (5 mM) increased total oxidation (ASP + CO2) more than oxidation to CO2. KCN (1.5 mM) inhibited more than 90% of the oxidation. NH4Cl inhibited the oxidation that reached a maximum at about 40 mM, but the inhibition of oxidation to CO2 (63%) was larger than that of total oxidation (30%). Carnitine did not influence NH4+ inhibition, which is consistent with the results reported for isolated mitochondria. Salicylate effects depended on salicylate concentration as well as on the presence of carnitine. In the absence of carnitine, inhibition of total oxidation reached 90% at 3 mM salicylate but that of oxidation to CO2 reached 50%. Velocity calculated at saturating palmitic acid concentration for total oxidation was slightly increased by 0.75 mM salicylate, but the increase for oxidation to CO2 was larger. At 3 mM salicylate, velocity at saturating palmitic acid concentration for the oxidation was decreased, but the decrease for oxidation to CO2 was smaller than for total oxidation. Carnitine partially relieved the inhibition of total oxidation and further increased the formation of CO2. The combination of 20 mM NH4Cl and 0.75 mM salicylate inhibited total oxidation, which was more than additive of the individual effects, and carnitine partially relieved the inhibition. It is concluded that NH4+ exerted a stronger inhibition of oxidation to CO2 than of oxidation to ASP, whereas salicylate strongly inhibited the oxidation to ASP but increased the oxidation to CO2 by uncoupling mitochondrial oxidative phosphorylation. Therefore, hyperammonemia and aspirin ingestion can inhibit fatty acid oxidation and mitochondrial metabolism that could lead to the pathophysiology seen in some childhood diseases such as Reye's syndrome. Carnitine therapy might offer some benefits.
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PMID:Effects of ammonium chloride, salicylate, and carnitine on palmitic acid oxidation in rat liver slices. 291 25

In rats, chronic ethanol feeding was found to enhance the postprandial hyperlipemia and to increase the incorporation of dietary palmitic acid-(3)H and intravenously injected L-lysine-(14)C into serum lipoproteins. The main increases of total amount, labeling, and specific activity of lipid and protein occurred in the d < 1.019 lipoprotein fraction. Fat absorption and the clearance of injected chylomicrons were not affected by ethanol feeding. Blocking of lipoprotein and chylomicron removal with Triton did not prevent the action of ethanol on serum lipids, indicating that the ethanol effect is not likely due to defective removal of lipids from the circulation. Ethanol enhanced the incorporation of chylomicron fatty acids into newly synthetized very low density lipoproteins, as shown by an increased reappearance of the fatty acid label into the lipids of this fraction after injection of palmitate-(14)C/glycerol-(3)H doubly labeled chylomicrons. These results indicate that alcoholic hyperlipemia is due, at least in part, to an increase in newly synthetized lipoproteins. The hyperlipemia produced by ethanol was accompanied by hepatic steatosis. The simultaneous production of fatty liver and hyperlipemia makes it unlikely that defective lipoprotein synthesis or secretion is a primary mechanism for the pathogenesis of the alcoholic fatty liver.
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PMID:Efcts of chronic ethanol feeding on serum lipoprotein metabolism in the rat. 544 77

The in vivo effects of pantethine were investigated on serum lipids and platelet lipid and platelet functions in 31 diabetic patients with hyperlipidemia. Pantethine decreased cholesterol from 236 +/- 62 mg/dl (M +/- SD) to 217 +/- 51 mg/dl (p less than 0.01) and increased high density lipoprotein cholesterol from 40 +/- 11mg/dl to 43 +/- 15 mg/dl. The diabetic platelets were larger when accompanied by higher microviscosity that healthy platelets. The characteristics of lipid composition in diabetic platelets were high levels of free cholesterol, phospholipid, triglyceride, cholesterol ester, palmitoleic acid, linoleic acid and palmitoleic acid/palmitic acid and low levels of the molar ratio of free cholesterol/phospholipids, phosphatidylethanolamine, oleic acid, arachidonic acid and oleic acid/stearic acid. Pantethine normalized these values of fatty acids to the control levels, and concomitantly reduced significantly the hyperaggregation of platelets induced by 10(6) M ADP and the hyper-ADP release reaction from platelets when exposed to 2 microgram of collagen, and made the volume smaller and the microviscosity lower after oral administration. From these data, it was concluded that pantethine normalized the abnormalities of serum lipids as well as platelet lipid compositions and subsequently reduced the hyper-aggregation and hyper-release reactions through the changes of volume and microviscosity of the platelets in diabetes mellitus with hyperlipidemia.
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PMID:Influence of pantethine on platelet volume, microviscosity, lipid composition and functions in diabetes mellitus with hyperlipidemia. 725 94

To clarify the relationship between lipid and glucose metabolism abnormalities in fructose-fed rats, we examined whether an improvement of insulin sensitivity by troglitazone (CS-045) or a decrease in plasma lipids by bezafibrate affects the relationship between serum levels of lipid and glucose. In addition, we also examined changes in liver glycogen metabolism and beta-oxidation in fructose-fed rats. Troglitazone ameliorated fasting hyperlipidemia, hyperglycemia, and hyperinsulinemia. In addition, it augmented glycogen synthase activity by 53%, and decreased the mitochondrial palmitic acid beta-oxidation rate and ketone body production rate by 27% and 55%, respectively. However, hyperglycemia and liver glycogen synthase activity were not improved by bezafibrate treatment despite a marked reduction of serum triglyceride (TG) levels resulting from a 1.76-fold increase in mitochondrial oxidation and a 2.04-fold increase in hepatic ketone body production. These results suggest that abnormalities in glucose and lipid metabolism in fructose-fed rats, which are ameliorated by troglitazone, may be closely linked to reduced glycogen synthase activity in the liver.
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PMID:Effect of troglitazone (CS-045) and bezafibrate on glucose tolerance, liver glycogen synthase activity, and beta-oxidation in fructose-fed rats. 878 34

The effects of positional distribution of triacylglycerol (TAG) fatty acids to TAG structures in chylomicrons and VLDL, and to postprandial lipemia, were studied in 10 healthy premenopausal women using a 6-h oral fat load test and a randomized, double-blind cross-over design. Molecular level information of TAG regioisomerism was obtained with a tandem mass spectrometric method. The positional distribution of fatty acids in chylomicron TAGs was similar to the respective dietary fat; 79% of the analyzed regioisomers in palm oil and 84% of the analyzed regioisomers in transesterified oil were found in chylomicron TAGs 3 h after the oral fat loads. VLDL TAGs were equal after the two fat loads in all but one regioisomer. Similarities in the fatty acid compositions of chylomicron TAGs suggest that palmitic acid was absorbed equally from both test fats. The proportion of palmitoleic acid in the chylomicrons was increased. Fat with palmitic acid predominantly in the sn-1 and sn-3 positions caused a larger incremental area of total TAGs in plasma and reduced plasma insulin values at the beginning of the postprandial response (0-90 min) compared with fat with palmitic acid randomly distributed. The relationship between TAG molecular structures in dietary fats and in lipoproteins provides new means for understanding the effects of fatty acid positional distribution on human lipid metabolism.
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PMID:Effects of palm oil and transesterified palm oil on chylomicron and VLDL triacylglycerol structures and postprandial lipid response. 1159 Feb 18

Neutral endopeptidase (NEP), a membrane-bound metallopeptidase enzyme that degrades neuropeptides, bradykinin, atrial natriuretic factor, enkephalins, and endothelin may regulate response to injury. We have previously demonstrated increased NEP localization and enzyme activity in diabetic wounds and skin compared with normal controls. We hypothesized that hyperlipidemia and hyperglycemia associated with type 2 diabetes mellitus may induce excessive NEP activity and thereby diminish normal response to injury. Human microvascular endothelial cells were treated with five different fatty acids (40 microM) with varying degrees of saturation, including oleic acid, linoleic acid, palmitic acid, stearic acid, and linolenic acid and/or glucose (40 mM) for 48 h. The effect of the antioxidative agents vitamin E and C on NEP enzyme activation was determined by treating the cultured cells with alpha-tocopherol succinate and/or L-ascorbic acid. Cell membrane preparations were assayed for NEP activity by incubation with glutaryl-Ala-Ala-Phe-4-methoxy-beta naphthylamide to generate a fluorescent degradation product methoxy 2 naphthylamine. High glucose or fatty acid concentration upregulated NEP activity. The highest NEP activity was observed with combined elevated glucose, linoleic acid, and oleic acid (P < 0.05). Antioxidant vitamin E and C treatment significantly reduced NEP enzyme activity after fatty acid exposure (P < 0.05). Thus, hyperglycemia and hyperlipidemia associated with type 2 diabetes mellitus may increase endothelial cell NEP activity and thereby decrease early pro-inflammatory responses. The modulator effect of vitamin E and C on NEP membrane enzyme activity after exposure to fatty acid stimulation suggests that lipid oxidation may activate NEP.
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PMID:Fatty acids and glucose increase neutral endopeptidase activity in human microvascular endothelial cells. 1278 4

Alterations in chylomicron and VLDL TAG and the magnitude of postprandial lipemia were studied in healthy volunteers after two meals of equal FA composition but different TAG FA positional distribution. Molecular level information of individual lipoprotein TAG regioisomers was obtained with a tandem MS method. The incremental area under the response curve of VLDL TAG was larger (P = 0.021) after modified lard than after lard. In plasma TAG, the difference did not quite reach statistical significance (P = 0.086). In general, there were less TAG with palmitic acid in the sn-2 position and more TAG with oleic acid in the sn-2 position in chylomicrons than in fat ingested. From 1.5 to 8 h postprandially, the proportion of individual chylomicron TAG was constant or influenced by TAG M.W. VLDL TAG regioisomerism was similar regardless of the positional distribution of fat ingested. Significant alterations were seen in VLDL TAG FA, in M.W. fractions, and in individual regioisomers with respect to time. The TAG sn-14:0-18:1-18:1 + sn-18:1-18:1-14:0, sn-16:0-16:1-18:1 + sn-18:1-16:1-16:0, and sn-16:1-18:1-18:1 + sn-18:1-18:1-16:1 decreased (P < 0.05); and sn-16:0-16:0-18:2 + sn-18:2-16:0-16:0, sn-16:0-16:0-18:1 + sn-18:1-16:0-16:0, sn-16:0-18:1-16:0, and sn-16:0-18:1-18:2 + sn-18:2-18:1-16:0 increased (P < 0.05) after both meals. In conclusion, positional distribution of TAG FA was found to affect postprandial lipid metabolism in healthy normolipidemic subjects.
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PMID:Chylomicron and VLDL TAG structures and postprandial lipid response induced by lard and modified lard. 1450 32

PGC-1alpha mRNA and protein are elevated in islets from multiple animal models of diabetes. Overexpression of PGC-1alpha impairs glucose-stimulated insulin secretion (GSIS). However, it is not well known which metabolic events lead to upregulation of PGC-1alpha in the beta-cells under pathophysiological condition. In present study, we have investigated effects of chronic hyperlipidemia and hyperglycemia on PGC-1alpha mRNA expression in isolated rat islets. Isolated rat islets are chronically incubated with 0, 0.2 and 0.4 mM oleic acid/palmitic acid (free fatty acids, FFA) or 5.5 and 25 mM glucose for 72 h. FFA dose-dependently increases PGC-1alpha mRNA expression level in isolated islets. FFA also increases PGC-1alpha expression in mouse beta-cell-derived beta TC3 cell line. In contrast, 25 mM glucose decreases expression level of PGC-1alpha. Inhibition of PGC-1alpha by siRNA improves FFA-induced impairment of GSIS in islets. These data suggest that hyperlipidemia and hyperglycemia regulate PGC-1alpha expression in islets differently, and elevated PGC-1alpha by FFA plays an important role in chronic hyperlipidemia-induced beta-cell dysfunction.
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PMID:Free fatty acids increase PGC-1alpha expression in isolated rat islets. 1573 55

The effect of Sargassum polycystum crude extract on lipid metabolism was examined against acetaminophen-induced (800 mg/kg body wt., intraperitoneally) hyperlipidemia during toxic hepatitis in experimental rats. The animals intoxicated with acetaminophen showed significant elevation in the levels of cholesterol, triglycerides and free fatty acid in both serum and liver tissue. The levels of tissue total lipids and serum LDL-cholesterol were also elevated with depleted levels of serum HDL-cholesterol and tissue phospholipid. The acetaminophen-induced animals showed significant alterations in the activities of lipid metabolizing enzymes serum lecithin cholesterol acyl transferase (LCAT) and hepatic triglyceride lipase (HTGL). The levels of liver tissue fatty acids (saturated, mono and polyunsaturated) such as palmitic acid, stearic acid, oleic acid, linoleic acid, arachidonic acid and linolenic acid monitored by gas chromatography were considerably altered in acetaminophen intoxicated animals when compared with control animals. The prior oral administration of Sargassum polycystum (200 mg/kg body wt./day for a period of 15 days) crude extract showed considerable prevention in the severe disturbances of lipid profile and metabolizing enzymes triggered by acetaminophen during hepatic injury. Liver histology also showed convincing supportive evidence regarding their protective nature against fatty changes induced during acetaminophen intoxication. Thus the present study indicates that the protective nature of Sargassum polycystum extract may be due to the presence of active compounds possessing antilipemic property against acetaminophen challenge.
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PMID:Effect of Sargassum polycystum (Phaeophyceae)-sulphated polysaccharide extract against acetaminophen-induced hyperlipidemia during toxic hepatitis in experimental rats. 1613 89


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