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Biomedical subjects

C A Drevon

Publications and source records attributed to C A Drevon.

At least 73 records · Page 4Linked to original sources
PubMed1995

Omega-3 fatty acids--nutritional aspects.

Omega-3 fatty acids contain a double bond in the third position from the methyl group. The very long-chain (20 or 22 carbon atoms) omega-3 fatty acids are mostly found in fatty fish and fish oils. The omega-3 fatty acids are essential and may act as precursors for eicosanoids, altering membrane fluidity or binding to transcription factors. Dietary intake of omega-3 fatty acids reduces plasma concentration of triglycerides, probably by decreasing hepatic secretion of very low density lipoprotein (VLDL) and by increasing catabolism of chylomicrons. In addition, lipid peroxidation of omega-3 fatty acids may take place, with good and bad consequences. As the number of double bonds is high, the omega-3 fatty acids may easily react with oxygen radicals. We performed studies where 5 g/day of very long-chain omega-3 fatty acids was given as a supplement for four months along with vitamin E, whereas control groups received similar amounts of other oils. The unsaturation index was higher in fatty acids of LDL from individuals exposed to omega-3 fatty acids, and the amounts of cholesteryl esters and total lipids were lower compared with control LDL, whereas similar electrophoretic mobility and apolipoprotein B structure were observed. There was a decrease in the melting temperature of cholesteryl esters in omega-3 fatty acid-enriched LDL, but no change in the susceptibility of LDL to Cu2+ catalyzed lipid peroxidation, as measured by changes in amounts of lipid peroxides or in the uptake of LDL in macrophages.(ABSTRACT TRUNCATED AT 250 WORDS)

Eicosanoids↗
PubMed1995

Evaluation of a quantitative food frequency questionnaire used in a group of Norwegian adolescents.

OBJECTIVE: The study was conducted to assess the reproducibility and validity of a 190-item self-administered quantitative food frequency questionnaire, used in a nation-wide study of adolescents. DESIGN AND SUBJECTS: Reproducibility study; 103 11th grade students (18 years) completed the questionnaire twice, with a 6-week interval. Validation study; 49 11th grade students filled in the questionnaire and kept 7-day weighed food records. RESULTS: Spearman rank correlations between the nutrient intakes from the two questionnaires varied from 0.63 (sugar energy percentage) to 0.91 (alcohol). The median coefficient was 0.85. The first questionnaire produced generally higher nutrient intake estimates than the second. Correlations between nutrient intake values from the records and the questionnaire ranged from 0.14 (vitamin D, non-significant, cod liver oil not included) to 0.66 (monounsaturated fatty acids). The median coefficient was 0.52. Adjustment for energy intake did not materially affect the correlations. On average 41% of the subjects were classified in the same quartile in the questionnaire and the records, and 2% in the opposite quartiles. However, the percentage of subjects in the same/opposite quartiles for vitamin D and fibre were 33/12 and 22/6, respectively. CONCLUSIONS: It is concluded that the questionnaire is able to rank subjects according to the tested nutrients, except vitamin D and fibre.

Adolescent↗
PubMed1995

Dietary intake among Norwegian adolescents.

OBJECTIVE: The aim of the nationwide study on dietary behaviour of adolescents was to describe and evaluate dietary habits, and relate that to other lifestyle factors. DESIGN AND SUBJECT: 1564 students in secondary schools completed a self-administered quantitative food frequency questionnaire in a school setting. RESULTS: The questionnaire showed an average energy intake of 15.8 and 9.9 MJ among boys and girls, respectively. Nearly 31% of the energy was supplied by fat and 11.4% by sugar. The average daily intake of micronutrients exceeded the Norwegian recommendations, except for vitamin D and iron in girls. 13.4% of the students had breakfast twice a week or less. These students had a higher percentage of energy from fat and sugar, and a lower intake of micronutrients, than students eating breakfast more often. Students who were daily smokers or fairly inactive had higher energy percentage from fat and sugar and lower intake of fibre, than non-smokers or physically active students. CONCLUSION: Half of the students consumed a diet with too much fat and two-thirds consumed too much sugar as compared to the recommendations. The girls had a diet with a higher nutrient density and a lower fat energy percentage than the boys. Finally, it seemed as if a healthy lifestyle was associated with a healthy diet.

Adolescent↗
PubMed1995

Tetradecylthioacetic acid (a 3-thia fatty acid) decreases triacylglycerol secretion in CaCo-2 cells.

The effects of the hypolipidemic fatty acid analogue tetradecylthioacetic acid (TTA) on synthesis and secretion of lipoproteins in CaCo-2 cells were studied. Radiolabeled tetradecylthioacetic acid was absorbed and metabolized as efficiently as oleic acid, although a discrepancy in the metabolic fate was evident. Whereas tetradecylthioacetic acid was incorporated into cell-associated triacylglycerol to the same extent as normal fatty acids (e.g., oleic acid and palmitic acid), the amount of triacylglycerol secreted from cells incubated with tetradecylthioacetic acid was 8 to 10 times lower than the amount secreted from cells incubated with palmitic acid and oleic acid, respectively. On the other hand, there was an enhanced incorporation of tetradecylthioacetic acid into cell-associated and secreted phospholipids. Despite incorporation of tetradecylthioacetic acid into cellular triacylglycerol, unlike oleic acid, tetradecylthioacetic acid did not stimulate production of triacylglycerol-rich particles. Ultracentrifugation of basolateral media from cells incubated with tetradecylthioacetic acid revealed low amounts of triacylglycerol in the triacylglycerol-rich fraction (p < 1.006 g/ml), suggesting secretion of lipoproteins with a higher density than chylomicrons. However, the present study shows that the stimulated triacylglycerol secretion caused by oleic acid was inhibited in the presence of TTA. The decreased rate of triacylglycerol secretion from these cells was not accompanied by a stimulation of fatty acid oxidation. Based on these findings, we therefore suggest that tetradecylthioacetic acid mainly affects secretion of lipoproteins in CaCo-2 cells.

Cell Line↗
PubMed1995

Effect of a coffee lipid (cafestol) on regulation of lipid metabolism in CaCo-2 cells.

The influence of cafestol, a lipid component found in boiled coffee, on low density lipoprotein (LDL) and lipid metabolism was investigated in CaCo-2 cells cultured on filter membranes. The rate of uptake and degradation of 125I-labeled tyramine cellobiose-LDL was increased 50% in CaCo-2 cells incubated with cafestol (20 micrograms/ml, 63 microM) for 24 h, whereas in cells incubated with 25-hydroxycholesterol (10 micrograms/ml, 25 microM) the rate of uptake and degradation showed a 30% decrease. A mixture of kahweol and cafestol, both natural components of coffee beans, modestly enhanced the rate of LDL uptake and degradation, as compared to pure cafestol. Incubation of cafestol with CaCo-2 cells induced a 3-fold up-regulation of LDL receptor mRNA, as compared to control cells. In contrast, incubation of the cells with 25-hydroxycholesterol produced a 30% decrease of LDL receptor expression. CaCo-2 cells were transfected with a promoter region containing the sterol regulatory element-1 (SRE-1) coupled to the reporter gene chloramphenicol acetyltransferase (CAT). When cells transfected with SRE-1 promoter were incubated with cafestol, there was a 20% up-regulation of CAT activity, whereas 25-hydroxycholesterol abolished this activity. Cafestol contributed to a significantly lowered secretion of cholesteryl ester and triacylglycerol, regardless of the radiolabeled precursor used ([2-14C]acetic acid, [1,2,3-3H]glycerol, [3H]water, and [1-14C]oleic acid). This reduction in secretion of lipids was accompanied by an increase in trichloroacetic acid-soluble activity when radiolabeled oleic acid was used as a tracer. We conclude that cafestol promotes an enhanced rate of uptake and degradation of LDL, probably due to an increase in transcription of LDL receptor mRNA and a reduced secretion of cholesteryl ester and triacylglycerol in CaCo-2 cells.

Cell Line↗
PubMed1994

Effect of n-3 and n-6 fatty acids on proliferation and differentiation of promyelocytic leukemic HL-60 cells.

Promyelocytic leukemic HL-60 cells were incubated with different fatty acids. Arachidonic acid (AA; 20:4, n-6) and eicosapentaenoic acid (EPA; 20:5, n-3) were the most potent inhibitors of proliferation in a dose-dependent way. Retinoic acid (RA) was used as a positive control. Inhibitors of cyclooxygenase and lipoxygenase or addition of antioxidants did not influence the effect of EPA or AA on cell proliferation. Increased capacity to generate superoxide anions after phorbol ester treatment and a reduced serglycin messenger RNA level in cells treated with AA or EPA indicated that these fatty acids induced differentiation in HL-60 cells similar to that induced by RA. However, down-regulation of the c-myc mRNA level, also typical for differentiation with RA in HL-60 cells, was not observed in cells incubated with AA or EPA. Flow cytometric analyses showed that in cultures incubated with AA or EPA, the proportion of cells in the G1 phase of the cell cycle increased. Similar effects were observed with RA. By flow cytometry and light scatter analyses it could be shown that AA made 8% of the cells apoptotic and 7% necrotic. The corresponding numbers were 21% and 10% for RA-treated cells, and 19% and 32% for EPA-treated cells. The present study shows that AA and EPA reduce the proliferation rate of HL-60 cells. This is mediated by mechanisms independent of eicosanoids or lipid peroxidation products and is due to effects both on apoptosis/necrosis and cell differentiation.

Apoptosis↗
PubMed1994

Effect of chronic incubation of CaCo-2 cells with eicosapentaenoic acid (20:5, n-3) and oleic acid (18:1, n-9) on triacylglycerol production.

CaCo-2 monolayers, cultured for 1 week after reaching confluence, were incubated with micellar solutions of fatty acids for up to 7 days. These conditioned cells were incubated acutely (5 h) with eicosapentaenoic acid and oleic acid, and the levels of cell-associated and secreted triacylglycerol were determined. With acute addition of oleic acid, both cell-associated and secreted triacylglycerol were decreased in cells chronically exposed to eicosapentaenoic acid. This effect was observed after as little as 2 days of chronic incubation with eicosapentaenoic acid. A further decrease was found when these cells were incubated acutely with eicosapentaenoic acid, regardless of which radioisotopes were used to label precursors in the incubation media. The secretion of both labelled and total triacylglycerol and apolipoprotein B was reduced approximately 50% in cells incubated chronically with eicosapentaenoic acid. The amounts of triacylglycerol and apolipoprotein B within the cells were not decreased by chronic exposure to eicosapentaenoic acid. Our data indicate that CaCo-2 cells chronically incubated with eicosapentaenoic acid secrete significantly less triacylglycerol than cells incubated chronically with oleic acid. When eicosapentaenoic acid was also included acutely, triacylglycerol secretion was reduced even more. We conclude that chronic exposure of eicosapentaenoic acid to this intestinal cell type reduces the rate of chylomicron secretion and may help explain the decreased postprandial lipaemia observed in humans taking fish oil supplements.

Adenocarcinoma↗
PubMed1994

[The significance of proteoglycans in several diseases].

A prominent feature in several diseases is the accumulation of connective tissue. The ultimate result of high levels of extracellular matrix is organ failure and death, evident in diseases such as liver fibrosis, diabetes and amyloidosis. Among the extracellular matrix components, proteoglycans play a basic role in several pathological conditions. In the development of atherosclerosis they provide an anchor for lipoprotein lipase on the endothelial wall, sequester lipoproteins in the subendothelial matrix and present lipoproteins to macrophages. In diabetes these proteoglycans have a lower charge, such that the network has a reduced capacity to retain negatively charged proteins. In fibrosis and amyloidosis the synthesis of proteoglycans and matrix is increased and large amounts are deposited at the expense of tissue-specific cells. Some of the conditions mentioned can be ameliorated by changes in the diet.

Amyloidosis↗
PubMed1994

Effect of cholesterol feeding on the susceptibility of lipoproteins to oxidative modification.

In previous studies we have shown that the liver endothelial and Kupffer cells in hypercholesterolemic rabbits are very active in endocytosis of low-density lipoprotein (LDL) and beta-very-low-density lipoprotein (beta-VLDL) (Nenseter et al. (1992) J. Lipid Res. 33, 867-877; Gudmundsen et al. (1993) J. Lipid Res. 34, 589-600). These data raised the question whether subfractions of LDL and beta-VLDL were modified in vivo to forms recognized by the scavenger/oxidized LDL receptors of the non-parenchymal liver cells. The purpose of the present study was to address this question by assessing the effect of cholesterol feeding on the susceptibility of the lipoproteins to oxidative modification in vitro. In addition, the effect of HDL on the lipid peroxidation of LDL was evaluated. LDL and beta-VLDL were isolated from rabbits given a diet supplemented with cholesterol (2% w/w) for 3 weeks. The extent of Cu(2+)-catalyzed oxidation of the lipoproteins was compared with that of LDL from control-fed rabbits. Extent of oxidation assessed by formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances, relative electrophoretic mobility and uptake of lipoproteins by J774 macrophages suggested that LDL and beta-VLDL from the hypercholesterolemic rabbits were more susceptible to oxidation than LDL from normolipidemic rabbits. HDL protected LDL and beta-VLDL from lipid peroxidation in vitro. Taken together, the increased susceptibility of LDL and beta-VLDL to oxidative modification in vitro, combined with the low levels of alpha-tocopherol, and the reduced ratio of HDL to LDL cholesterol observed in the hypercholesterolemic rabbits, and the protective effect of HDL on the lipid peroxidation of LDL, support the probability that oxidative modification of LDL and beta-VLDL occur in vivo in the hypercholesterolemic rabbits.

Animals↗
PubMed1994

Fatty acid uptake and metabolism in CaCo-2 cells: eicosapentaenoic acid (20:5(n-3)) and oleic acid (18:1(n-9)) presented in association with micelles or albumin.

In vivo, long-chain fatty acids are incorporated into bile salt micelles, which solubilize the hydrophobic fatty acids before they are transported across the unstirred water layer to the intestinal brush border membrane. In the present study we have used CaCo-2 cells, cultured on filter membranes as a model of human enterocytes, and compared presentation of fatty acids bound to albumin with a micellar form. Absorption of eicosapentaenoic acid and oleic acid from micellar solutions was 4-times faster than from fatty acid-albumin complexes after 5 h incubation, and resulted in a corresponding increase in triacylglycerol synthesis and secretion. Mass determination of newly synthesized, cell-associated triacylglycerol after 5 h incubation, indicated a 5-fold increase in cells exposed to a micellar solution versus albumin-complexed fatty acids. A 2-fold larger fraction of the absorbed fatty acids was incorporated into triacylglycerol than into phospholipids when the fatty acids were presented as micelles. Analysis by resistive pulse technique showed that secreted lipoproteins of density less than 1.006 g/ml were in the same size-range as chylomicrons derived from human plasma. In spite of an increased amount of secreted triacylglycerol from cells supplemented with micellar fatty acids, there was no increase in the mean size of these particles. Synthesis and secretion of triacylglycerol in cells exposed to eicosapentaenoic acid and oleic acid were similar regardless of whether the fatty acids were presented to the cells associated with albumin or micelles, although the total amount of triacylglycerol synthesized and secreted was highest with micelles. When incubating CaCo-2 monolayers with eicosapentaenoic acid or oleic acid bound to albumin, a similar amount of radioactivity was released as CO2 and acid soluble products into the medium with less than 3% of the lipids being oxidized after 5 h of incubation. The oxidation rate of fatty acids in cells incubated with micelles was increased 40 to 100%. In conclusion, micellar fatty acids are absorbed, metabolized and influence secretion of lipoprotein particles to a higher extent than albumin-bound fatty acids in CaCo-2 cells, and there is no major difference between eicosapentaenoic acid and oleic acid.

Albumins↗
PubMed1993

Very long chain n-3 and n-6 polyunsaturated fatty acids inhibit proliferation of human T-lymphocytes in vitro.

The effect of marine n-3 polyunsaturated fatty acids on proliferation of human T-cells in vitro was compared to other polyunsaturated, monounsaturated and saturated fatty acids. Monoenes and saturated fatty acids had little effect on T-cell proliferation. Eicosapentaenoic acid and docosahexaenoic acid exerted a strong dose-dependent inhibitory effect on proliferation of mitogen- or antigen-stimulated T-cells, similar to that observed for arachidonic acid. Sixty microM of albumin-bound eicosapentaenoic acid or arachidonic acid promoted 25-40% inhibition of proliferation of T-cells stimulated with mitogen, whereas the same concentration of albumin-bound docosahexaenoic acid promoted 60% inhibition. When epidermal cells (Langerhans cells) were used as antigen-presenting cells, 100 microM of albumin-bound eicosapentaenoic acid or arachidonic acid caused 40% inhibition on T-cell proliferation. Low density lipoprotein (LDL), isolated after four months of dietary intake of fish oil or corn oil, inhibited mitogen-stimulated T-cell proliferation in a dose-dependent manner. Fish oil- and corn oil-enriched LDL showed similar ability to inhibit T-cell proliferation. Epidermal cells preincubated with docosahexaenoic acid, and extensively washed before adding purified T-cells and antigen, resulted in a strong inhibition of T-cell proliferation, whereas preincubation of purified T-cells with docosahexaenoic acid did not cause any inhibitory effect. Cyclooxygenase and lipoxygenase inhibitors (indomethacin, acetylsalicylic acid, nordihydroguaertic acid) did not affect the antiproliferative effect of eicosapentaenoic acid and arachidonic acid, neither did the antioxidants butylated hydroxytoluene or alpha-tocopherol. Eicosanoids, (PGE2, PGE3, LTB4, LTB5 and lipoxin A or lipoxin B) added directly to mitogen-stimulated peripheral blood mononuclear cells (PBMC) did not influence T-cell proliferation significantly. Decreased viability was observed when mitogen-stimulated lymphocytes were cultured with essential polyunsaturated fatty acids, whereas the viability of unstimulated lymphocytes was hardly influenced by the same fatty acids. We conclude that; (a) pharmacological albumin-bound concentrations of the highly unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid promote a strong antiproliferative effect on mitogen- and antigen-stimulated human T-cells: (b) docosahexaenoic acid can suppress accessory cell function and consequently suppress T-cell activation; (c) physiologic concentration of LDL particles rich in n-3 and n-6 fatty acids, both promote a dose-dependent antiproliferative effect on mitogen-stimulated PBMC; (d) the inhibition is independent of eicosanoid metabolites; and (e) lipid peroxidation seems unlikely to be responsible for the antiproliferative effect.

Dose-Response Relationship, Drug↗
PubMed1993

Dietary supplementation of very long-chain n-3 fatty acids decreases whole body lipid utilization in the rat.

Rats were fed lard or n-3 fatty acid-supplemented diets ad libitum to study whole body oxidation of lipid and carbohydrate. One group of male rats was fed 21% fat (by weight) containing 19.5% lard and sufficient amounts of essential fatty acids (1.5%). Another group of rats had 6.5% of the lard replaced by ethyl esters of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The rats were fed these diets for 6-8 weeks. Body weight gain was similar for the two groups and absorption of fat was complete in animals fed both types of fatty acids. Indirect calorimetric measurements, after 3-5 weeks on these diets, by continuous registration of O2 consumption and CO2 formation showed no difference in mean energy expenditure during the experimental period. However, the mean respiratory quotient (RQ) was significantly increased for animals fed the n-3 fatty acid-supplemented diet. This was noted both under fasting conditions and after receiving a test meal of similar fatty acid composition for both feeding groups. Thus, mean substrate utilization demonstrated reduced oxidation of fat and increased oxidation of carbohydrate, during fasting as well as fed periods for the n-3 fatty acid group as compared to the lard group. After an additional 2-3 weeks, blood plasma, liver, and muscle samples were collected, and adipocytes and hepatocytes were isolated. Reduced postprandial plasma concentrations of triacylglycerol, phospholipids, unesterified fatty acids, and glycerol were promoted by the n-3 fatty acid diet as compared to lard. Plasma concentration of glucose was slightly increased, and liver and muscle content of glycogen were decreased in the n-3 fatty acid-fed rats. Experiments with isolated adipocytes showed decreased basal lipolysis after feeding n-3 fatty acids for 6-8 weeks for suspended epididymal adipocytes, whereas stimulated lipolysis by isoproterenol (0.1 microM) was higher in both epididymal and mesenteric adipocytes from rats fed n-3 fatty acids as compared to animals fed lard. In addition, epididymal adipocytes from rats fed n-3 fatty acids were significantly smaller than cells from animals fed lard. Hepatic peroxisomal fatty acid oxidation was significantly higher for n-3 fatty acid-supplemented animals, but total fatty acid oxidation was similar in both dietary groups. The hepatic content of triacylglycerol and phospholipids was similar for both diets. These results demonstrate that n-3 fatty acid replacement of a high-fat diet containing mostly saturates and monoenes for several weeks promotes reduced use of fat as energy source. This may be explained by decreased plasma concentration of unesterified fatty acids.(ABSTRACT TRUNCATED AT 400 WORDS)

Adipose Tissue↗
PubMed1992

Serum lipids, hepatic glycerolipid metabolism and peroxisomal fatty acid oxidation in rats fed omega-3 and omega-6 fatty acids.

Rats were fed, for 3 weeks, high-fat (20% w/w) diets containing sunflower-seed oil, linseed oil or fish oil. Chow-fed rats were used as a low-fat reference. The high-fat diets markedly reduced non-fasting-rat serum triacylglycerol as compared with the low-fat reference, and the highest reduction (85%) was observed with the fish-oil group, which was significantly lower than that of the other high-fat diets. The serum concentration of phospholipids was significantly reduced (30%) only in the fish-oil-fed animals, whereas serum non-esterified fatty acids were reduced 40-50% by both the fish-oil- and linseed-oil-fed groups. The liver content of triacylglycerol showed a 1.7-fold increase with the fish-oil diet and 2-2.5-fold with the other dietary groups when compared with rats fed a low-fat diet, whereas the hepatic content of phospholipids was unchanged. Peroxisomal fatty acid oxidation (acyl-CoA oxidase) was 2-fold increased for the rats fed fish oil; however this was not significantly higher when comparison was made with rats fed the linseed-oil diet. There was no difference in phosphatidate hydrolysis (microsomal and cytosolic fractions) among animals fed the various diets. Acyl-CoA:diacylglycerol acyltransferase activity was increased by all high-fat diets, but the fish-oil-diet-fed group showed a significantly lower enzyme activity than did rats fed the other high-fat diets. A linear correlation between acyl-CoA:diacylglycerol acyltransferase activity and liver triacylglycerol was observed, and the microsomal enzyme activity was decreased 40-50% by incubation in the presence of eicosapentaenoyl-CoA. CoA derivatives of arachidonic, linolenic and linoleic acid had no inhibitory effect when compared with the control. These results indicate that dietary fish oil may have greater triacylglycerol-lowering effect than other polyunsaturated diets, owing to decreased triacylglycerol synthesis caused by inhibition of acyl-CoA:diacylglycerol acyltransferase. In addition, increased peroxisomal fatty acid oxidation and decreased availability of non-esterified fatty acids could also contribute by decreasing the amounts of fatty acids as substrates for triacylglycerol synthesis and secretion.

Acyltransferases↗