Cafestol (a coffee lipid) decreases uptake of low-density lipoprotein (LDL) in human skin fibroblasts and liver cells.
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Biological Transport↗
Biomedical subjects
C A Drevon
Publications and source records attributed to C A Drevon.
Omega-3 and omega-6 fatty acids in the insulin resistance syndrome. Lipid and lipoprotein metabolism and atherosclerosis.
Dietary fatty acids appear to be of significant importance for several of the most-common diseases in modern societies. To obtain more knowledge about the health consequences of dietary fatty acids, we depend upon a better understanding of the mechanisms of action of these fatty acids in vivo. With regard to the IRS, omega-3 PUFA may exert beneficial effects upon many of the associated pathophysiological metabolic changes. Omega-3 PUFA reduce fasting and postprandial TG, may improve insulin sensitivity (as shown in animal experiments), decrease platelet and leukocyte reactivity, alter immunological functions, and may slightly decrease blood pressure. Omega-3 PUFA may also beneficially influence vessel wall characteristics and blood rheology. Furthermore, both types of PUFA (omega-3 and omega-6) have been shown to inhibit cardiac arrhythmias in animals. The role of omega-3 PUFA in blood clotting and fibrinolysis still remains controversial, whereas omega-6 fatty acids may lead to increased oxidation of lipoproteins. Regardless of the effects on LDL oxidizability, both types of PUFA have shown beneficial effects on the development of atherosclerosis. As yet, little is known about the effect of specific omega-6 fatty acids with respect to the IRS. Potential adverse effects of dietary PUFA must not be neglected, but should be viewed in light of the beneficial effects of these agents.
Animals↗
Expression of human cholesterol 7alpha-hydroxylase in atherosclerosis-susceptible mice via adenovirus infection.
Adenovirus is a vector for the delivery of genes mainly to the liver. Short-term (approximately 3 days) studies using adenovirus transfection have provided valuable insights into how genes can complement normal and pathological phenotypes. When atherosclerosis-susceptible C57BL/6 mice were infected with an adenovirus vector containing the human 7alpha-hydroxylate cDNA (AV17h1) and fed on a chow diet, human 7alpha-hydroxylase mRNA and enzyme activity doubled compared with that in mice infected with an adenovirus vector (AV1Null) alone. In AV17h1-infected mice fed on a high fat cholic acid (HFCA) diet, mRNA expression and activity of both the endogenous and adenovirus (human) 7alpha-hydroxylase were repressed. AV17h1-infected mice fed on a HFCA diet and killed at mid-light had increased 7alpha-hydroxylase activity and mRNA compared with mice killed at mid-dark. Since expression of AV17h1 is driven by a constitutive Rous sarcoma virus promoter, the repression of human 7alpha-hydroxylase by the HFCA diet was unexpected. In spite of this post-transcriptional repression by the HFCA diet, AV17h1-infected mice expressed the human 7alpha-hydroxylase mRNA, causing its enzyme activity to be 3-fold greater than in AV1Null-infected mice. In AV17h1-infected mice, the 7alpha-hydroxylase enzyme activity varied as a linear function of human mRNA abundance. In conclusion, the accumulation of apolipoprotein B-containing lipoproteins in plasma of C57BL/6 mice fed on the HFCA diet was not reduced by longer-term (2 weeks) 7alpha-hydroxylase expression, probably because of its diminished expression caused by the diet and hepatic inflammation from the adenovirus infection. These results may suggest that adenovirus is effective in promoting longer-term (2 weeks) expression of 7alpha-hydroxylase.
Adenoviridae Infections↗
[Proteoglycans and pathology--new aspects].
It is well documented that proteoglycans are involved in a wide range of pathological conditions. Recently published results in international journals provide new information on the role of proteoglycans in such conditions. A mutation in the gene encoding for a cell surface proteoglycan has been demonstrated in overgrowth syndromes. A proteoglycan has been isolated from urine and shown to induce cachexia in cancer patients. Furthermore, in both achondrogenesis and colon cancer, the reduced ability to sulphate proteoglycans is due to genetic defects in cellular sulfate transporters. Finally, fibrosis has been inhibited in glomerulonephritic mice by transferring the gene for decorin, a transforming growth factor beta-1 binding proteoglycan, into muscle tissue.
Animals↗
Response rates with different distribution methods and reward, and reproducibility of a quantitative food frequency questionnaire.
OBJECTIVES: To evaluate the use of a self-administered quantitative food frequency questionnaire (QFFQ) in a national dietary survey concerning (a) response rates with different distribution methods and reward; (b) degree of underreporting of energy intake; (c) reproducibility of the QFFQ; and (d) seasonal variation on reported intake. DESIGN AND SUBJECTS: A pilot study was performed in 1992 to test response rates to the QFFQ with three different distribution methods, with and without reward, in a random sample of 1200 adults aged 16-79 y. In another study, the QFFQ was distributed to a nation-wide, representative random sample of 5008 adults aged 16-79 y during June, September, November 1993 and March 1994. Reproducibility was evaluated among 90 responders to the survey who answered another QFFQ six weeks later. RESULTS: The distribution method combining postal distribution and collecting the QFFQ by interviewer as well as an offer to participate in a lottery, gave the highest response rate (72%). The possibility to get a reward increased the response rate by 9, 14 and 57%, respectively, depending on the distribution method used. The mean daily energy intake and the percentage of subjects claiming to have unlikely low energy intake did not differ significantly between the different ways of distribution. In the main survey the mean ratio between energy intake and estimated basal metabolic rate was 1.58 among men and 1.47 among women, and 37% of men and 45% of women had a ratio below 1.35. Spearman rank correlations between the two QFFQ ranged from 0.48 (edible fats) to 0.91 (coffee) with a median coefficient of 0.70. For nutrients correlations ranged from 0.55 (carbohydrate E%) to 0.81 (alcohol), with a median coefficient of 0.72. The season of questionnaire administration was of minor importance for the reported intake of the main foods and nutrients. CONCLUSIONS: The QFFQ-method is suitable for use in a Norwegian nutritional surveillance system. SPONSORSHIP: National Nutrition Council, Ministry for Agriculture, Ministry for Health and Social Affairs and Norwegian Research Council.
Adolescent↗
Effect of coffee lipids (cafestol and kahweol) on regulation of cholesterol metabolism in HepG2 cells.
We studied the effect of the coffee diterpene alcohols, cafestol and kahweol, on cholesterol metabolism in HepG2 cells. Uptake of 125I-tyramine cellobiose-labeled LDL was decreased by 15% to 20% (P < .05) after 18 hours of preincubation with cafestol (20 micrograms/mL), whereas 25-hydroxycholesterol reduced uptake by 55% to 65% (P < .05). Degradation of LDL in the presence of cafestol was decreased by 20% to 30% (P < .05) under the same conditions. The effect of cafestol (20 micrograms/mL) on uptake and degradation of LDL was greatest (35% to 40%, P < .05) after 6 and 10 hours of preincubation, respectively. Furthermore, the effect of cafestol was also dependent on its concentration, and a significant decrease in the LDL uptake (19%) was observed at 10 micrograms/mL (P < .05). Specific binding of LDL was reduced by 17% (P < .05) and 60% (P < .05) after preincubation with cafestol (20 micrograms/mL) and 25-hydroxycholesterol (5 micrograms/mL) for 6 hours, respectively, compared with control cells. Analysis of LDL binding showed that cafestol reduced the number of binding sites for LDL on the cell surface (capacity) by 35% (P < .05). In contrast, no significant effect on the level of mRNA for the LDL receptor was observed after incubation with cafestol, whereas 25-hydroxycholesterol reduced the mRNA level for the LDL receptor by 40% to 50% (P < .05). A fusion gene construct consisting of a synthetic sterol regulatory element-1 (SRE-1) promoter for the human LDL receptor coupled to the reporter gene for chloramphenicol acetyltransferase (CAT) was transfected into HepG2 cells. No change was observed in CAT activity in SRE-1-transfected cells after incubation with cafestol, whereas 25-hydroxycholesterol reduced CAT activity by 30% to 40% (P < .05). Incorporation of [14C]acetate into unesterified cholesterol and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity were unaffected in cells incubated with cafestol as well as the cafestol-kahweol mixture compared with control cells. Moreover, cafestol and the cafestol-kahweol mixture did not promote increased incorporation of radiolabeled [14C]oleic acid into cholesteryl esters after short-term incubation compared with control cells. On the other hand, 25-hydroxycholesterol caused a 70% to 90% reduction of cholesterol synthesis (P < .05) and HMG-CoA reductase activity (P < .05), decreased HMG-CoA reductase mRNA level by 70% to 80% (P < .05), and promoted a twofold increase in cholesterol esterification (P < .05). Finally, no effect of the coffee diterpenes on bile acid formation was observed. These results suggest that cafestol (and kahweol) may reduce the activity of hepatic LDL receptors and thereby cause extracellular accumulation of LDL.
Bile Acids and Salts↗
Peroxidation of LDL from combined-hyperlipidemic male smokers supplied with omega-3 fatty acids and antioxidants.
The effects of marine omega-3 polyunsaturated fatty acids (FAs) and antioxidants on the oxidative modification of LDL were studied in a randomized, double-blind, placebo-controlled trial. Male smokers (n = 41) with combined hyperlipidemia were allocated to one of four groups receiving supplementation with omega-3 FAs (5 g eicosapentaenoic acid and docosahexaenoic acid per day), antioxidants (75 mg vitamin E, 150 mg vitamin C, 15 mg beta-carotene, and 30 mg coenzyme Q10 per day), both omega-3 FAs and antioxidants, or control oils. LDL and human mononuclear cells were isolated from the patients at baseline and after 6 weeks of supplementation. LDL was subjected to cell-mediated oxidation by the patients' own mononuclear cells, as well as to Cu(2+)-catalyzed and 2,2'-azobis-(2-amidinopropane hydrochloride) (AAPH)-initiated oxidation. Extent of LDL modification was measured as lag time, the formation rate of conjugated dienes (CDs), the maximum amount of CDs formed, formation of lipid peroxides, and the relative electrophoretic mobility of LDL on agarose gels. Dietary supplementation with omega-3 FAs increased the concentration of total omega-3 FAs in LDL and reduced the concentration of vitamin E in serum. The omega-3 FA-enriched LDL particles were not more susceptible to Cu(2+)-catalyzed, AAPH-initiated, or autologous cell-mediated oxidation than control LDL. In fact, enrichment with omega-3 FAs significantly reduced the formation rate of CDs when LDL was subjected to AAPH-induced oxidation. Supplementation with moderate amounts of antioxidants significantly increased the concentration of vitamin E in serum and increased the resistance of LDL to undergo Cu(2+)-catalyzed oxidation, measured as increased lag time, reduced formation of lipid peroxides, and reduced relative electrophoretic mobility compared with control LDL. Supplementation with omega-3 FAs/antioxidants showed oxidizability of LDL similar to that of control LDL and omega-3 FA-enriched LDL. In conclusion, omega-3 FAs neither rendered the LDL particles more susceptible to undergo in vitro oxidation nor influenced mononuclear cells' ability to oxidize autologous LDL, whereas moderate amounts of antioxidants protected LDL against oxidative modification.
Administration, Oral↗
N-3 fatty acids and chylomicron metabolism in the rat.
Dietary n-3 fatty acids (FAs) reduce postprandial triacylglycerol concentrations in humans by unknown mechanisms. Our goals were to reproduce this phenomenon in the rat, and then to determine the mechanism. In an oral fat tolerance study two groups of rats were fed diets containing 2.1% ethyl esters of n-3 FA or olive oil for 2 weeks. After gavaging with emulsified soybean oil, the postprandial chylomicron triacylglycerol levels in the n-3 FA group were reduced by 40% (P < 0.05). The hypothesis that n-3 FA feeding reduced chylomicron production/secretion from the gut was tested by blocking chylomicron removal with Triton WR1339 before gavaging the rats with the fat load. This completely eliminated the hypochylomicronemic effect suggesting that chylomicron input was not inhibited by n-3 FAs. Chylomicron clearance was studied by injecting chylomicrons containing radioactive retinyl esters and triacylglycerol into rats from both groups. Pre-feeding with n-3 FAs accelerated the removal of chylomicron triacylglycerol and retinyl esters from the plasma with significantly lower fractions of dose remaining at 2, 4, and 8 min post-injection for both tracers. These findings suggest than n-3 FAs reduce postprandial chylomicronemia in the rat by accelerating chylomicron lipid clearance.
Animals↗
Effect of hormone replacement therapy on the susceptibility of low-density lipoprotein to oxidation among postmenopausal hypercholesterolaemic women.
The effect of sequential combined hormone replacement therapy on the susceptibility of low-density lipoprotein to oxidative modification was investigated in a double-blind, randomized placebo-controlled study. Hypercholesterolaemic, postmenopausal women were supplemented with 17 beta-oestradiol and norethisterone acetate (n = 13 subjects) or placebo capsules (n = 15 subjects) for 12 weeks. They were instructed to follow the American Heart Association step one diet. Low-density lipoprotein, isolated before and after treatment, was subjected to copper-catalysed lipid peroxidation. There were no significant differences between low-density lipoprotein from the hormone replacement therapy and placebo groups, as assessed by measuring the lag time for formation of conjugated dienes, the rate of formation and the amount of conjugated dienes formed, the amount of lipid peroxides generated, and the relative electrophoretic mobility at baseline and after treatment. Dietary records showed that the subjects were consuming similar amounts of fat and vitamins. No major differences were found in the fatty acid pattern of low-density lipoprotein from the two groups. In conclusion, the results indicated that hormone replacement therapy with 17 beta-oestradiol sequentially combined with norethisterone acetate in non-smoking, hypercholesterolaemic, postmenopausal women has no protective effect on the susceptibility of low-density lipoprotein to copper-catalysed modification in vitro.
Adult↗
Very-long-chain n-3 fatty acids as biomarkers for intake of fish and n-3 fatty acid concentrates.
We examined how supplementation with very-long-chain n-3 fatty acids was reflected in the concentration of these fatty acids in plasma phospholipids of 363 Norwegian men and women. The concentration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in plasma phospholipids was significantly higher among individuals supplemented with n-3 fatty acids after the supplementation period than before. We also examined the relation between dietary intake of fatty acids measured with a 180-item quantitative food-frequency questionnaire and the concentration of the same fatty acids in plasma phospholipids in 579 men and women. Correlation coefficients between plasma phospholipid fatty acids and dietary intake of fatty acids were 0.51 and 0.49 for EPA and DHA, respectively. The correlation between fish intake and n-3 fatty acids in plasma phospholipids was 0.37. These results suggest that dietary intake measured with our food-frequency questionnaire may be used to predict the biological availability of some of the essential n-3 fatty acids.
Adolescent↗
Dietary polyunsaturates and peroxidation of low density lipoprotein.
Oxidative modification of low density lipoprotein is influenced by dietary polyunsaturates. Omega-6 polyunsaturated fatty acids enhance the susceptibility of low density lipoprotein to oxidation compared with monoenes. Most studies on omega-3 fatty acids also exhibit increased peroxidation of low density lipoprotein, although these data are more conflicting. Future studies should focus on additional information concerning dietary intake of antioxidants, fatty acids and lipid peroxides, as well as on the importance of low density lipoprotein oxidation in vivo.
Animals↗
The Norwegian diet during the last hundred years in relation to coronary heart disease.
OBJECTIVE: The influence of dietary changes on serum cholesterol and CHD during the last century in Norway has been evaluated. DESIGN: Data on food consumption are based on national food supply and household consumption surveys. To be able to calculate comparable series of the dietary content of energy, fat, saturated, monounsaturated and polyunsaturated fatty acids and dietary cholesterol, we compiled food composition data covering this century. The dietary effect on serum cholesterol was estimated by Keys equation. RESULTS: Changes in dietary lipids precede the increase and the decrease in mortality of CHD. The estimated serum cholesterol level in the population increased by approximately 1 mmol/l during 1900-1960, and decreased by approximately 0.6 mmol/l during 1960-1992. These changes correspond to a 60% increase and a 30% decrease in risk for CHD. However, the observed change in mortality of CHD was greater. During 1951-1955 and 1971-1975 it increased by 120% in men and 80% in women aged 50-59 years and during 1971-1975 and 1991-1993 it decreased by 43% and 29%, respectively. CONCLUSIONS: Change in dietary lipids have the potential to explain a great deal of the changes in mortality of CHD in Norway during this century. A reduced consumption of boiled coffee and an increase in the consumption of antioxidants may also have contributed to the reduced mortality of CHD the last 20 years.
Cholesterol↗
Effect of homocysteine on copper ion-catalyzed, azo compound-initiated, and mononuclear cell-mediated oxidative modification of low density lipoprotein.
Homocysteine is an independent risk factor for cardiovascular diseases. The mechanisms by which elevated plasma concentrations of homocysteine are related to the pathogenesis of atherosclerosis are not fully understood. To examine whether homocysteine is implicated in atherogenesis through the modification of low density lipoprotein (LDL), the effect of homocysteine on the oxidation of LDL was studied by three different oxidation systems. Thus, LDL was subjected to Cu(2+)-catalyzed, azo compound-initiated, and peripheral blood mononuclear cell-mediated oxidative modification. The extent of modification was assessed by measuring the formation of conjugated dienes, lipid peroxides, thiobarbituric acid-reactive substances, and the relative electrophoretic mobility. Homocysteine at a normal plasma concentration (6 microM) showed no effect, whereas a concentration corresponding to moderate hyperhomocysteinemia (25 microM) or to concentrations seen in homocystinuria patients (100, 250, and 500 microM) protected LDL from modification of the lipid as well as of the protein moiety. One exception was observed: when the oxidation was initiated by copper ions, homocysteine at concentrations 6 and 25 microM stimulated the lipid peroxidation of LDL to a small, but statistically significant extent. High concentrations of homocysteine showed antioxidative properties as long as the thiol groups were intact, thereby delaying the onset of the oxidation. The 1,1-diphenyl-2-picrylhydracyl radical test demonstrated that homocysteine at concentrations > or = 50 microM possessed marked free radical scavenging capacity. Finally, LDL isolated from two patients with homozygous homocystinuria showed similar extent of Cu(2+)-catalyzed oxidation as LDL from a group of healthy control subjects. Taken together, our data suggest that low concentrations of homocysteine in the presence of copper ions may enhance the lipid peroxidation of LDL, whereas high concentrations of homocysteine may protect LDL against oxidative modification in the lipid as well as in the protein moiety. Thus, homocysteine-induced atherosclerosis may be explained by mechanisms other than oxidative modification of low density lipoprotein.
Adolescent↗
[Fat-soluble vitamins in clinical practice].
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Humans↗
[Fat-soluble vitamins in clinical practice].
The identification of fat-soluble vitamins at the beginning of this century had a major impact on human health. The classical deficiency symptoms could be treated with effective means. After a period of rather low interest in fat-soluble vitamins, we are now in the midst of a new wave of research on these vitamins, with a large number of reports in influential international journals. It has been demonstrated that the fat-soluble vitamins have many more functions than previously known, and suboptimal status has been linked to several diseases. In this review, we describe these new aspects of the fat-soluble vitamins A, D, E and K.
Avitaminosis↗
Fatty acid pattern of esterified and free fatty acids in sera of women with normal and pre-eclamptic pregnancy.
OBJECTIVE: To determine the composition of esterified and free fatty acids in sera of women with normal and pre-eclamptic pregnancy. SETTING: Department of Obstetrics and Gynaecology, Aker Hospital, Oslo, Norway. SUBJECTS: Blood samples were taken from 510 healthy nulliparae at a gestational age of 17-19 weeks. Nineteen of these subsequently developed pre-eclampsia. Seventeen of these, for whom blood samples were still available, and a control group of 17 women taken from the same population and matched for age, body mass index, gestational age and parity, were later studied in detail. A further group of 29 women admitted to the hospital with pre-eclampsia were also studied, as was a matched control group of 29 women with normal pregnancies recruited from the antenatal clinic. METHODS: Blood samples were drawn after 8 to 10 h fasting. The patterns of serum free fatty acids and esterified fatty acids were determined by thin-layer chromatography combined with gas-liquid chromatography. Free fatty acids were also determined enzymatically. RESULTS: Among the circulating free fatty acids, the levels of palmitic (16:0), oleic (18:1 n-9) and linoleic acids (18:2 n-6) were significantly higher early in pregnancy in women who later developed pre-eclampsia. The same free fatty acids were also significantly increased in women with pre-eclampsia. The level and composition of the esterified fatty acids in phospholipids, triglycerides and cholesteryl esters did not, however, differ between the two groups early in pregnancy. In contrast, in women with pre-eclampsia, the relative content of oleic acid was increased in the phospholipid fraction, whereas linoleic acid was decreased in the phospholipid and triglyceride fractions. CONCLUSIONS: We observed that the level and composition of circulating free fatty acids were already altered 10-20 weeks before the clinical onset of pre-eclampsia. When the disease became overt there were changes in both esterified and free fatty acids.
Adult↗
Paracetamol inhibits copper ion-induced, azo compound-initiated, and mononuclear cell-mediated oxidative modification of LDL.
The effects of paracetamol and sodium salicylate on the susceptibility of LDL to oxidative modification were studied. LDL was subjected to Cu(2+)-, azo compound-, or peripheral blood mononuclear cell-initiated oxidation in the absence and presence of paracetamol and salicylate. Paracetamol (100 mumol/L; 25 micrograms LDL/mL) reduced the rate of formation of conjugated dienes and the amount of conjugated dienes formed during Cu(2+)-induced oxidation by 67% and 58%, respectively. Paracetamol (400 mumol/L; 100 micrograms LDL/mL) reduced the generation of lipid peroxides during Cu(2+)-induced oxidation by 43% (P < .05), the relative electrophoretic mobility in agarose gels by 16% (P < .05), and the amount of oxidized LDL taken up by J774 macrophages by 22% (P < .05). Paracetamol (100 mumol/L; 100 micrograms LDL/mL) reduced the 2,2'-azobis-(2-amidinopropane hydrochloride)-initiated lipid peroxidation by 70% (P < .05) and the relative electrophoretic mobility by 34% (P < .05). Paracetamol (100 mumol/L; 100 micrograms LDL/mL) reduced the amount of lipid peroxides generated in LDL during mononuclear cell-mediated oxidation by 69% (P < .01) and the relative electrophoretic mobility by 38% (P < .01). In comparison, 10 mumol/L alpha-tocopherol reduced the amount of lipid peroxides formed during cellular LDL oxidation and the relative electrophoretic mobility by 52% and 65%, respectively (P < .05). In the absence of paracetamol, SOD and catalase inhibited the modification of LDL (P < .05), suggesting that superoxide anions and hydrogen peroxide might be involved in the cell-mediated modification pathway. In the presence of paracetamol, SOD showed no additional inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Acetaminophen↗
No effect of beta-carotene supplementation on the susceptibility of low density lipoprotein to in vitro oxidation among hypercholesterolaemic, postmenopausal women.
The effect of beta-carotene on the susceptibility of low density lipoprotein (LDL) to oxidative modification was investigated in a double-blind, randomized placebo-controlled study. Hypercholesterolaemic, postmenopausal women were given 30 mg beta-carotene per day (n = 15 subjects) or placebo capsules (n = 15 subjects) for 10 weeks. They were instructed to follow the American Heart Association Step One diet. LDL, isolated before and after treatment was subjected to copper-catalysed lipid peroxidation. There were no significant differences between LDL from the beta-carotene and placebo groups, as assessed by measuring the lag time for formation of conjugated dienes; the rate of formation and the amount of conjugated dienes formed; the amount of lipid peroxides generated; and the relative electrophoretic mobility, at baseline and after treatment. Dietary records showed that the subjects were consuming similar amounts and types of fat. No significant differences were found in the lipid composition and fatty acid pattern of LDL from the two groups. In conclusion, the results indicated that supplementation with beta-carotene in non-smoking, hypercholesterolaemic, postmenopausal women had no protective effect on the susceptibility of LDL to copper-catalysed modification in vitro.
Adult↗