Comparison of the effects of dietary n-3 and n-6 polyunsaturated fatty acids on very-low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnants.
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The effects of chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids (derived from fish or corn oil respectively) on the secretion of very-low-density lipoprotein (VLDL) lipid and apolipoprotein B (apoB) by rat hepatocytes in culture was investigated. Remnants were prepared in vivo from chylomicrons obtained from rats given an oral dose of fish or corn oil and incubated with cultured hepatocytes for up to 16 h. The medium was then removed and the secretion of cholesterol and triacylglycerol into the whole medium or the rho<1.050 g/ml fraction during the following 7-24 h was determined. After exposure of the cells to fish-oil as compared with corn-oil remnants, secretion of both cholesterol and triacylglycerol into the whole medium was decreased by 25-35%, and secretion into the rho<1.050 g/ml fraction was decreased by 20-25%. In addition, the levels of apoB48 found in the rho<1.050 g/ml fraction were significantly lower in cells treated with fish-oil rather than corn-oil remnants, although the levels of apoB100 remained unchanged. The expression of mRNA for apoB, as determined by reverse-transcriptase PCR, however, was not significantly changed after exposure of the cells to both types of remnants. These results demonstrate that the effects of dietary n-3 polyunsaturated fatty acids in depressing hepatic VLDL secretion occur directly when they are delivered to the liver from the intestine in chylomicron remnants, and that the secretion, but not the synthesis, of apoB is targeted. (+info)
Corn oil-induced decrease in arterial thrombosis tendency may be related to altered plasma vitamin K transport.
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In this article we report the effects of low and high fat diets on the arterial thrombosis tendency in rats. The animal system used was the aorta loop model, in which we compared the effect of saturated (hardened coconut oil, HCO) and unsaturated (sunflower seed oil, SSO; corn oil, CO) fatty acids on the arterial thrombosis tendency at high fat intake (50 energy%, 45 energy% of which was either HCO, SSO, or CO). Under these conditions both SSO and CO had a beneficial effect (relative to HCO) on the arterial thrombosis tendency. In a subsequent study we compared these high fat diets with a low fat diet (5 energy%). As compared with the low fat diet, only CO significantly decreased the thrombosis risk. Serum vitamin K and triglycerides had decreased substantially after the CO diet, and to a much lesser extent after the SSO diet. It is concluded that corn oil may have a mildly anticoagulant effect, the potential benefit of which is discussed. (+info)
Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol.
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BACKGROUND: Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis. OBJECTIVE: The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infarction (MI) on subsequent cardiac events and serum lipids. DESIGN: Three hundred patients with acute MI were randomly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil, administered in a double-blind manner over 12-24 mo. Median follow-up time was 1.5 y. Clinical follow-up, including the drawing of blood samples, was performed after 6 wk of treatment and later at 0.5-year intervals. RESULTS: Forty-two (28%) patients in the n-3 group and 36 (24%) in the corn oil group experienced at least one cardiac event (cardiac death, resuscitation, recurrent MI, or unstable angina). No significant difference in prognosis was observed between groups for single or combined cardiac events. Total cholesterol concentrations decreased in both groups, with no significant intergroup differences. On average, the monthly increase in HDL cholesterol was 1.11% in the n-3 group and 0.55% in the corn oil group (P = 0.0016). Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group, whereas they increased by 0.35%/mo in the corn oil group (P < 0.0001). CONCLUSION: No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids. (+info)
Olive oil decreases both oxidative stress and the production of arachidonic acid metabolites by the prostaglandin G/H synthase pathway in rat macrophages.
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Fish oil has a preventive role in cardiovascular and inflammatory diseases, but little is known about the effect of olive oil, which is widely consumed in Mediterranean regions. We examined the influence of dietary olive oil, corn oil and fish oil-rich diets on the production of superoxide anion (O2-) and nitric oxide (.NO) by resident macrophages stimulated by phorbol 12-myristate 13-acetate (PMA) and their effect on arachidonic acid release, prostaglandin G/H synthase-2 (PGHS-2) expression and the subsequent prostaglandin E(2) production. Resident peritoneal macrophages stimulated by PMA from rats fed with olive oil or corn oil had the same level of O2- production, but these levels were increased by the fish oil diet. Olive oil and the fish oil diets increased .NO and decreased arachidonic acid mobilization and the production of prostaglandin E(2). PGHS-2 expression, however, was not affected by diet. We conclude that although olive oil and fish oil reduce arachidonic acid mobilization and subsequent metabolism through the PGHS-2 pathway in PMA-stimulated macrophages, only olive oil offers an additional beneficial effect by increasing .NO/O2- production. (+info)
Effects of fatty acids and growth hormone on liver fatty acid binding protein and PPARalpha in rat liver.
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The aim of this study was to investigate the interaction between long-chain fatty acids (LCFA) and growth hormone (GH) in the regulation of liver fatty acid binding protein (LFABP) and peroxisome proliferator-activated receptor-alpha (PPARalpha). Cultured rat hepatocytes were given oleic acid (OA; 500 microM) and GH (100 ng/ml) for 3 days. LFABP mRNA increased 3.6-fold by GH and 5.7-fold by OA, and combined incubation with GH and OA increased LFABP mRNA 17.6-fold. PPARalpha mRNA was decreased 50% by GH, but OA had no effect. Hypophysectomized (Hx) female rats were treated with L-thyroxine, cortisol, GH, and dietary fat for 7 days. PPARalpha mRNA levels were three- to fourfold higher in Hx than in normal female rats. GH decreased PPARalpha mRNA 50% in Hx rats. Dietary triglycerides (10% corn oil) increased LFABP mRNA and cytosolic LFABP about twofold but had no effect on PPARalpha mRNA in Hx rats. GH and dietary triglycerides had an additive effect on LFABP expression. Dietary triglycerides increased mitochondrial hydroxymethylglutaryl-CoA synthase mRNA only in the presence of GH. The diet increased serum triglycerides in Hx rats, and GH treatment prevented this increase. Addition of cholesterol to the diet did not influence LFABP levels but mitigated increased hepatic triglyceride content. In summary, these studies show that GH regulates LFABP expression independently of PPARalpha. Moreover, GH has different effects on PPARalpha-responsive genes and does not counteract the effect of LCFA on the expression of these gene products. (+info)
Regulation of rat carboxylesterase expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD): a dose-dependent decrease in mRNA levels but a biphasic change in protein levels and activity.
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Carboxylesterases play an important role in the metabolism of endogenous lipids and foreign compounds; therefore, xenobiotic regulation of carboxylesterase gene expression has both physiological and pharmacological significance. We previously reported that beta-naphthoflavone and 3-methylcholanthrene, two potent inducers for cytochrome P4501A enzymes, had opposing effects on the expression of hydrolase S, a secretory carboxylesterase. Beta-naphthoflavone caused suppression, whereas 3-methylcholanthrene caused induction of the expression of this enzyme. The aim of the present study was to determine the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), another prototypical cytochrome P4501A inducer, on the expression of this and several other rat carboxylesterases (hydrolases A, B, and C) in liver and extrahepatic tissues. Rats received TCDD treatment at nonlethal (+info)
The treatment of purified maize oil bodies with organic solvents and exogenous diacylglycerol allows the detection and solubilization of diacylglycerol acyltransferase.
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In spite of its importance in the biosynthesis of reserve oils in plants, diacylglycerol acyltransferase (DAGAT, EC 2.3.1.20) has not been purified to homogeneity, and its study has remained incomplete. We found that the microsomal preparations from developing maize embryos contained substantial amounts of endogenous diacylglycerol (DAG). A solubilization procedure for extracting DAGAT from the microsomes (D. Little, R. Weselake, K. Pomeroy, S.T. Furukawa, J. Bagu, Biochem. J. 304 (1994)) was ineffective in eliminating the endogenous DAG, even after gel filtration. DAG removal through the preparation of acetone powders from the embryos led to the loss of DAGAT activity. Labelled triacylglycerol (TAG) was produced in the standard DAGAT assay when labelled DAG was supplied in benzene solution to the freeze-dried microsomes and the sample was dried and resuspended in an aqueous buffer. In contrast, no labelled TAG was produced when a similar sample supplied with non-labelled DAG was assayed with emulsified labelled DAG and acyl-CoA. Repeated washing of the microsomal freeze-dried fraction with benzene resulted in a complete loss of DAGAT activity in the standard assay, but the activity was restored by the addition of DAG plus phosphatidylcholine or Tween 20 in benzene. Although DAGAT has been reported to be confined mainly to the endoplasmic reticulum, we found that DAGAT activity was high in the purified oil bodies from both developing and mature maize embryos and was not removed by repeated washing with 6 M urea. The DAGAT activity was restored from delipidated oil bodies and from microsomes after the preparations had been resuspended in methanol/acetic acid/water (1:1:1, v/v). Although most of the proteins in the suspension were eluted as a single peak at the void volume after gel filtration chromatography, DAGAT activity was found in later fractions. SDS-PAGE of the peak activity fraction revealed no protein bands after silver staining, and the finding suggest that DAGAT protein is of low abundance and has a high k(cat). (+info)
Prophylaxis of hemodialysis graft thrombosis with fish oil: double-blind, randomized, prospective trial.
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Diets enriched with fish oil may favorably affect the vascular perturbations underlying synthetic graft thrombosis. Therefore, these studies were designed to test the hypothesis that diets enriched with fish oil would decrease the incidence of thrombosis in newly constructed polytetrafluorethylene grafts. A double-blind, randomized trial was conducted. Twenty-four patients were randomized to receive 4000 mg of fish oil or 4000 mg of control oil. Both preparations were enriched with antioxidants and deodorized with peppermint. Patients began therapy within 2 wk after graft placement and were monitored for 12 mo or until thrombosis developed. With a permuted-block randomization schedule, 12 patients received fish oil and 12 patients received control oil. The primary patency rates at 365 d were 14.9% for the control group and 75.6% for the fish oil-treated group. Survival analysis revealed a significant difference between fish oil-treated and untreated patients (P < 0.03, Mantel-Cox test), with a power of 90%. Moreover, analysis of covariables, including age of > or =50 yr, gender, race, body weight, diabetes mellitus, bleeding times, and lipid profiles, indicated that this effect occurred principally as a result of fish oil administration. Importantly, fish oil treatment also decreased venous outflow resistance and systemic BP, compared with control values. Fish oils possess unique biologic properties that favorably affect the incidence of polytetrafluorethylene graft thrombosis, and they thus represent a potential treatment strategy for the prevention of access thrombosis. (+info)