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Biomedical subjects

C A Drevon

Publications and source records attributed to C A Drevon.

At least 19 recordsLinked to original sources
PubMed1999

Doxazosin treatment and peroxidation of low-density lipoprotein among male hypertensive subjects: in vitro and ex vivo studies.

Doxazosin is an antihypertensive drug that gives rise to 6- and 7-hydroxydoxazosin during hepatic metabolism. The structures of the hydroxymetabolites suggest that they may possess antioxidative properties. The aim of the present study was to examine whether doxazosin and 6- and 7-hydroxydoxazosin were able to scavenge free radicals and whether these compounds might protect low-density lipoprotein (LDL) against in vitro and ex vivo oxidation. Both 6- and 7-hydroxydoxazosin showed radical scavenging capacity as assessed by measuring scavenging of 1,1-diphenyl-2-picrylhydrazyl radicals. In vitro incubation with 10 microM 6- and 7-hydroxydoxazosin significantly reduced human mononuclear cell-mediated oxidation of LDL, measured as the formation of lipid peroxides and the relative electrophoretic mobility of LDL (to 10 and 6% of the control, respectively). Furthermore, formation of conjugated dienes in LDL during Cu2+-induced oxidation was significantly reduced in the presence of 5 microM 6- and 7-hydroxydoxazosin (to 28% of tmax [time to maximum] of control). However, treatment of hypertensive patients with increasing doses of doxazosin (from 1 to 8 mg/day) for 8 weeks altered neither Cu2+-catalyzed, 2,2'azobis-(2-amidinopropane hydrochloride)-initiated, nor cell-mediated oxidation of patient LDL ex vivo. Furthermore, the total antioxidative capacity of plasma was unaffected by treatment. In conclusion, the present study shows that 6- and 7-hydroxydoxazosin have radical scavenging properties and protect LDL against in vitro oxidation. However, treatment of hypertensive male subjects with increasing doses of doxazosin for 8 weeks did not affect ex vivo oxidation of LDL.

Adult↗
PubMed1999

Evaluation of a food frequency questionnaire with weighed records, fatty acids, and alpha-tocopherol in adipose tissue and serum.

The authors examined the validity of a self-administered 180-item food frequency questionnaire in 125 Norwegian men aged 20-55 years who filled in the questionnaire and completed 14-day weighed records in fall 1995 to winter 1995/6. Spearman correlation coefficients between the two measurements ranged from 0.42 for percent of energy from fat to 0.66 for sugar intake (median r = 0.51). On average, 39% of the men were classified in the same quartile with the two methods, and 3% in the opposite quartile. Correlation coefficients between intake of fatty acids estimated from the questionnaire and the relative amounts of fatty acids in adipose tissue were: linoleic acid (18:2, n-6), r = 0.38; alpha-linolenic acid (18:3, n-3), r = 0.42; eicosapentaenoic acid (20:5, n-3), r = 0.52; and docosahexaenoic acid (22:6, n-3), r = 0.49. The correlations for these fatty acids between the total serum lipids and the diet were 0.16, 0.28, 0.51 and 0.52, respectively. The data suggest that very-long-chain n-3 fatty acids in adipose tissue and total serum lipids reflect the dietary intake of very-long-chain n-3 fatty acids to the same degree. No associations were observed between intake of alpha-tocopherol and concentration in adipose tissue and serum.

Adipose Tissue↗
PubMed1999

[Leptin--a fatty tissue hormone with many functions].

The importance of genetic factors in obesity is under investigation. During the last few years, our understanding of the regulation of body weight in mammals has broadened to include several new proteins based on the cloning of genes from rodent mutants and characterization of their effects on energy stores and metabolism. Since its discovery in 1994, leptin has been acknowledged as an adipocyte-derived signal molecule, able to limit food intake and increase energy expenditure by interacting with specific leptin receptors located in the central nervous system and in peripheral tissues. Leptin is also important for growth, reproduction and neuroendocrine signalling. Although leptin is mainly synthesized in adipocytes, it is also expressed in the placenta, epithelium of the stomach and breast glands and, under certain conditions, in skeletal muscles. The importance of leptin is demonstrated by the discovery of mutations in the genes encoding leptin and its receptor among some subjects with morbid obesity and infertility. Plasma concentration of leptin should be measured in obese infertile adolescents since replacement could be curative among individuals with leptin deficiency.

Adipose Tissue↗
PubMed1999

Plasma homocysteine concentration related to diet, endothelial function and mononuclear cell gene expression among male hyperlipidaemic smokers.

BACKGROUND: Elevated plasma concentration of homocysteine is an independent risk factor for development of cardiovascular diseases. MATERIALS AND METHODS: We evaluated potential links between homocysteine and atherothrombogenesis by relating the plasma concentration of homocysteine to (i) dietary antioxidants and omega-3 fatty acids (and determined influence of intervention with antioxidants or omega-3 fatty acids); (ii) markers of endothelial cell function; and (iii) peripheral blood mononuclear cell mRNA levels. RESULTS: We observed an inverse relationship between the plasma homocysteine concentration and dietary intake of vegetables, vitamin C and beta-carotene and between homocysteine and the serum concentration of folate, vitamin B12 and omega-3 fatty acids. Intervention with antioxidants or omega-3 fatty acids did not affect plasma homocysteine concentration. The plasma levels of cysteinylglycine and vitamin B12 correlated positively with circulating E-selectin and VCAM-1, respectively, whereas folate in serum and blood correlated negatively with P-selectin. A negative correlation was found between the concentrations of homocysteine and von Willebrand factor. Negative and positive correlations were found between plasma homocysteine and the mononuclear cell mRNA levels of peroxisome proliferator activated receptor delta (PPAR delta) and c-myc respectively. A negative correlation was also found between plasma homocysteine and mononuclear cell mRNA levels of the proteoglycan serglycin. Homocysteine was not correlated with serum activity of glutathione peroxidase or with the mRNA level of glutathione peroxidase in mononuclear cells. CONCLUSION: The plasma homocysteine level was negatively correlated with dietary intake of vegetables, including vitamins C and E, and serum omega-3 fatty acids, whereas supplementation with antioxidants or omega-3 fatty acids did not affect plasma homocysteine concentration. Homocysteine was not associated with circulating adhesion molecules or increased procoagulant activity, but homocysteine may alter mononuclear cell gene expression. Cysteine showed no significant correlation with these parameters.

Adult↗
PubMed1998

Cell proliferation, apoptosis and accumulation of lipid droplets in U937-1 cells incubated with eicosapentaenoic acid.

The monocytic cell line U937-1 was cultured in the presence of eicosapentaenoic acid (20:5, n-3) (EPA) or oleic acid (18:1, n-9) (OA). EPA caused a dose-dependent inhibition of cell proliferation, whereas OA had no effect. At the highest EPA concentrations, 120 and 240 microM, inhibition of cell proliferation was accompanied by initiation of apoptosis. A concentration of 60 microM EPA caused a 35% reduction in cell proliferation without inducing apoptosis, and was therefore used for further studies. Addition of antioxidants or inhibitors of eicosanoid synthesis had no influence on the reduced cell proliferation after EPA treatment. The inhibition required continuous presence of EPA in the incubation medium as the cells resumed a normal proliferation rate when they were placed in EPA-free medium. The inhibition of proliferation was not accompanied by differentiation into macrophage-like cells, as expression of serglycin and the ability to perform respiratory burst was unaffected by EPA. Expression of CD23 mRNA increased when the cells were incubated with EPA, but to a smaller extent than after retinoic acid (RA) or PMA treatment. Furthermore, expression of the monocytic differentiation markers CD36 and CD68 was lower in cells treated with EPA or OA when compared with untreated cells. The cell cycle distribution of U937-1 cells was similar in cells incubated with EPA or PMA, whereas RA-treated cells accumulated in the G1 phase. Side scatter increased in cells incubated with EPA and OA, which was ascribed to an accumulation of lipid droplets after examination of the cells by electron microscopy. The number of droplets per cell was higher in cells exposed to EPA than OA. The cellular triacylglycerol (TAG) increased 5.5- and 15.5-fold after incubation with OA and EPA respectively. No difference in the cellular content of cholesterol compared with untreated cells was observed. The TAG fraction in EPA-treated cells contained high amounts of EPA and docosapentaenoic acid and minor amounts of docosahexaenoic acid, whereas OA-treated cells had high levels of OA in the TAG. In cells incubated with a sulphur-substituted EPA, only minor effects on cell proliferation and no accumulation of cellular TAG were observed. These findings may indicate the existence of other mechanisms for regulation of cell behaviour by very-long-chain polyunsaturated n-3 fatty acids than the well established lipid peroxide and eicosanoid pathways.

Antioxidants↗
PubMed1998

Proteoglycans in macrophages: characterization and possible role in the cellular uptake of lipoproteins.

The murine macrophage cell line J774 was incubated with [35S]sulphate. The cell-associated 35S-labelled macromolecules were shown to be proteoglycans and glycosaminoglycans in similar amounts. The possible presence of cell-surface proteoglycans was investigated by incubating [35S]sulphate-labelled cells with trypsin for 15 min. The released material contained approx. 70% free glycosaminoglycan chains and 30% proteoglycans. The latter component was demonstrated by HNO2 treatment to contain heparan sulphate. In the total cell fraction not treated with trypsin a small but significant portion was shown to be chondroitin sulphate proteoglycan. The cell-associated glycosaminoglycans contained both chondroitin sulphate and heparan sulphate. To investigate possible biological functions of cell-surface proteoglycans in macrophages, cells were incubated with NaClO3 to inhibit sulphation of proteoglycans and beta-d-xyloside to abrogate proteoglycan expression. The uptake of oxidized 125I-tyraminylcellobiose-labelled low-density lipoprotein (125I-TC-LDL) was typically two to three times higher than that of native 125I-TC-LDL in untreated J774 cells. The cellular uptake at 37 degreesC of native 125I-TC-LDL was decreased 25% after both NaClO3 and xyloside treatment, whereas the uptake of oxidized 125I-TC-LDL was decreased 35% after both types of treatment. The mRNA levels for the scavenger receptor A-II and the LDL receptor were not affected by NaClO3 or xyloside treatment. Furthermore, fluid-phase endocytosis, measured as uptake of horseradish peroxidase, and receptor-mediated endocytosis, measured as uptake of 125I-TC-ovalbumin, were not affected by NaClO3 treatment of J774 cells. Removal of cell-surface chondroitin sulphate with chondroitinase ABC decreased only the binding of native 125I-TC-LDL, whereas removal of heparan sulphate with heparitinase decreased the binding of both oxidized and native 125I-TC-LDL. Addition of lipoprotein lipase increased the uptake of oxidized 125I-TC-LDL 1.7 times and the uptake of native 125I-TC-LDL 2.1 times. The binding of the former was more sensitive to NaClO3 treatment than the latter. The results presented support the notion that some of the uptake pathways for lipoproteins in the foam-cell-forming macrophages depend on the presence of cell-surface heparan sulphate and chondroitin sulphate.

Animals↗
PubMed1998

Postprandial decrease in plasma unesterified fatty acids during n-3 fatty acid feeding is not caused by accumulation of fatty acids in adipose tissue.

Dietary supplementation of very long-chain n-3 fatty acids to rats reduces postprandial plasma concentrations of triacylglycerol, unesterified fatty acids and glycerol after long-term feeding by unknown mechanisms [Rustan et al., J. Lipid Res. 34 (1993) 1299-1309]. In the present study we examine the role of adipose tissues in metabolism of fatty acids. Postprandial plasma concentrations of triacylglycerol, unesterified fatty acids and glycerol were reduced by 75%, 50% and 30%, respectively, during 49 days of feeding high-fat diets containing n-3 fatty acids (6.5% n-3 fatty acid concentrate, 13% lard) as compared to lard (19.5% lard). These differences were observed already after two days of feeding. Plasma concentration of unesterified very long-chain n-3 fatty acids increased to 50 microM in n-3 fatty acid-supplemented rats, whereas these fatty acids were undetectable in lard-fed animals. The n-3 fatty acid-enriched diet limited cell volumes of perirenal and epididymal adipocytes by 40% and 30%, respectively, after 49 days, as compared to lard feeding. This reduction in cell volume was not due to reduced synthesis of glycerolipids in epididymal adipocytes. Acute incubation of perirenal and epididymal adipocytes with oleic acid or eicosapentaenoic acid, caused similar increase in synthesis of triacylglycerol. Dietary supplementation with n-3 fatty acids decreased basal and total lipolysis (isoprenalin-stimulated) in perirenal adipocytes. Basal lipolysis in epididymal adipocytes was reduced by n-3 fatty acids only after 49 days. n-3 fatty acids increased total lipolysis in mesenteric and subcutaneous fat cells compared to adipocytes derived from lard-fed animals, whereas basal lipolysis was unchanged. These results suggest that the reduced postprandial plasma concentration of unesterified fatty acids after n-3 fatty acid-supplementation is not caused by accumulation of fatty acids in adipose tissue. The reduced trophic growth of adipocytes might be due to decreased supply of unesterified fatty acids for triacylglycerol storage. (c) 1998 Elsevier Science B.V.

Adipose Tissue↗
PubMed1998

Intake of very-long-chain n-3 fatty acids related to social status and lifestyle.

OBJECTIVES: Little information is available about the intake of very-long-chain n-3 fatty acids in random samples of populations. We examined if the intake of these fatty acids was associated with gender, social status and lifestyle in a similar way as other indicators for a healthy diet in a nationwide survey. DESIGN AND SUBJECTS: Data were obtained from self-administered quantitative food frequency questionnaires filled in by a representative sample of Norwegian men and women, aged 16-79 y. 3144 (63%) of the invited subjects responded with acceptable questionnaires. RESULTS: Daily intake of very-long-chain n-3 fatty acids was on average 0.9 g/d and 0.4% of total energy was derived from these fatty acids. Energy derived from very-long-chain n-3 fatty acids was slightly higher among men than women, and two-fold higher among subjects aged 60-79 vs 16-29 y. White collar workers had higher intake of very-long-chain n-3 fatty acids than blue collar workers. Men and women in the highest quartile of intake of very-long-chain n-3 fatty acids had 2-3 E% higher fat intake (mostly mono- and polyunsaturated fatty acids), as compared to individuals in the lowest quartile. They also had 3-4 fold higher daily intake of retinol and vitamin D, as well as 20-50% higher intake of fruits and vegetables, dietary fibre and vitamin C. CONCLUSIONS: Intake of very-long-chain n-3 fatty acids was correlated to indicators for healthy dietary habits. However, contrary to many other indicators of a healthy diet, energy derived from very-long-chain n-3 fatty acids was not significantly associated with female gender or non-smoking.

Adolescent↗
PubMed1998

Fatty acid composition in maternal milk and plasma during supplementation with cod liver oil.

OBJECTIVE: We investigated how cod liver oil influences the amount of essential fatty acids in mothers' breast milk. DESIGN AND INTERVENTION: Lactating mothers (n =22) were randomized into four groups 3-8 weeks after parturition. They were supplemented for 14 days with 0, 2.5, 5 and 10 ml cod liver oil (7.7 g eicosapentaenoic acid (EPA, 20:5n-3), 10.2 g docosahexaenoic acid (DHA, 22:6n-3) and 22.9 g n-3 fatty acids in total per 100 ml). RESULTS: In maternal plasma phospholipids there was an increase in the content of EPA and DHA in the group supplemented with 10 ml cod liver oil daily (P < or = 0.05). DHA concentrations in breast milk pre-supplementation ranged from 0.15 to 1.56 wt% and increased in all supplemented groups (P< or =0.05). The concentration of EPA in breast milk increased in the groups supplemented with 5 or 10 ml cod liver oil (P< or =0.05), whereas the concentration of arachidonic acid (AA, 20:4n-6) did not change in any of the supplemented groups. Total intake of DHA adjusted to body mass index (BMI), correlated to DHA concentrations in plasma (r = 0.49, P = 0.02) and breast milk (r = 0.45, P = 0.04). The concentration of tocopherol did not change during the supplementation period, neither in plasma nor in breast milk. CONCLUSION: Dietary intake of DHA is reflected in the concentration of DHA in breast milk, without affecting the concentration of AA or tocopherol.

Adult↗
PubMed1998

Multiplication and death-type of leukemia cell lines exposed to very long-chain polyunsaturated fatty acids.

Polyunsaturated fatty acids (PUFA) may reduce cell multiplication in cultures of normal, as well as transformed, white blood cells. We assessed the sensitivity of 14 different leukemia cell lines to PUFA by measuring cell number after 3 days of incubation. Ten of the examined cell lines were sensitive to 30, 60 and/or 120 microM of arachidonic, eicosapentaenoic and docosahexaenoic acid, whereas four cell lines were resistant. The sensitivity to PUFA was not associated with any particular cell lineage, clinical origin or specific mRNA pattern of bcl-2 and c-myc. Effects on cell viability were assessed by studying cell membrane integrity, DNA fragmentation and cell morphology. The sensitive cell lines Raji and Ramos died by necrosis and apoptosis, respectively, during incubation with eicosapentaenoic acid, whereas the viability of the resistant U-698 cell line was unaffected. The effects of EPA on Raji cells, was counteracted by vitamin E, indicating that lipid peroxidation was involved. However, apoptosis induced by eicosapentaenoic acid in Ramos cells, was unaffected by vitamin E, as well as eicosanoid synthesis inhibitors. In conclusion, our results indicate that a majority of leukemia cell lines are sensitive to PUFA. This sensitivity may be caused by induction of apoptosis or necrosis by very long-chain polyunsaturated fatty acids.

Apoptosis↗
PubMed1998

Effects of omega-3 fatty acids and/or antioxidants on endothelial cell markers.

BACKGROUND: Increased expression of cell adhesion molecules and increased procoagulant activity of the vascular endothelium have been postulated to characterize dysfunctional endothelium. The cellular effects of n-3 fatty acids (n-3 FAs) and antioxidants are still not clarified. METHODS: In a randomized, factorial two-by-two design study, we have investigated 41 male smokers with hyperlipidaemia before and after 6 weeks of supplementation with either n-3 FAs (4.8 g daily) or placebo with the addition of antioxidants (150 mg of vitamin C, 75 mg of vitamin E and 15 mg of beta-carotene daily) or placebo with regard to the effects on some endothelial cell markers: thrombomodulin (sTM), von Willebrand factor (vWF), tissue plasminogen activator antigen (tPAag) and soluble forms of the cell adhesion molecules E-selectin, P-selectin and vascular cell adhesion molecule 1 (VCAM-1). RESULTS: In the n-3 FA group, significant reductions in the plasma levels of vWF (P = 0.034) and sTM (P < 0.001) were demonstrated compared with placebo, whereas increased levels were found for E-selectin (P = 0.001) and VCAM-1 (P = 0.010). In the antioxidant group, no differences in changes were noted for any of the variables. CONCLUSION: The reduction in the levels of sTM and vWF with n-3 FA supplementation could indicate an improvement with regard to the haemostatic markers of endothelial dysfunction, whereas the simultaneous increase in the soluble forms of E-selectin and VCAM-1 may suggest an adverse effect on the inflammatory system. The antioxidants seem to be neutral in their effect on these endothelial cell markers in our study population of smokers. The interpretation of the soluble forms of these molecules are, however, still debatable.

Adult↗
PubMed1998

Under- and overreporting of energy intake related to weight status and lifestyle in a nationwide sample.

Desire for weight change and level of dietary consciousness may severely bias reported food intake in dietary surveys. We evaluated to what degree under- and overreporting of energy intake (EI) was related to lifestyle, sociodemographic variables, and attitudes about body weight and diet in a nationwide dietary survey. Data were gathered by a self-administered quantitative food-frequency questionnaire distributed to a representative sample of men and women aged 16-79 y in Norway, of whom 3144 subjects (63%) responded. Reported EI was related to estimated basal metabolic rate (BMR) based on self-reported body weight, age, and sex. An EI:BMR < 1.35 was considered to represent underreporting and an EI:BMR > or = 2.4 as overreporting of EI. Fewer men than women underreported EI (38% compared with 45%). The fraction of overreporters did not differ significantly between sexes (7% of the men compared with 5% of the women). A large proportion of underreporters was obese (9%) and wanted to reduce their weight (41%). Few overreporters were obese and 12% wanted to increase their weight. Underreporters consumed fewer foods rich in fat and sugar than did the other subjects. Multiple regression analysis showed that desire for weight change and physical activity score were significantly correlated with both EI and EI:BMR when adjusted for sociodemographic and lifestyle variables. Our findings indicated that attitudes about one's own body weight influenced reported EI. These attitudes are important in the interpretation of dietary data because many of the subjects (> 30%) wanted to change their body weight.

Adolescent↗
PubMed1998

Leptin levels in pregnant women and newborn infants: gender differences and reduction during the neonatal period.

OBJECTIVE: Leptin is a highly hydrophilic protein that circulates in plasma as a 16-kDa protein. It is produced in adipose tissue and also recently described to be synthesized by placental tissue. Plasma concentration of leptin is positively correlated to body fat mass, and administration of recombinant leptin to mice indicates that leptin participates in the regulation of food intake and energy expenditure. Leptin may have a role during initiation of human pubertal development. Gender differences have been reported among adults as well as among children, even after correction for body fat content. Little is known about variation in leptin levels during pregnancy or the level or function of leptin in the growing fetus and infants. The aim of the present study was to examine plasma concentration of leptin in pregnant women and their newborn infants during the first 3 months of life, and to relate plasma leptin concentration to body weight and gender during this period. MATERIALS AND METHODS: Among 609 women recruited to study the effect of very long-chain n-3 fatty acids during pregnancy, 180 women were selected to study leptin as well. The women were all healthy and nulli- or primiparas, and 16% were smokers. The study was randomized and double-blinded, and the participants received either 10 mL of cod liver oil (Peter Moller, avd.av Orkla ASA, Oslo, Norway) daily or the same amount of corn oil. Blood samples were taken from the mothers during pregnancy in weeks 18 and 35, and from the umbilical cord and from 4- and 14-week-old infants. The mothers' body mass index (BMI) at 18 and 35 weeks of pregnancy was calculated by using body weight recorded within 1 week or, if this was missing, by using means from weights at the closest time points before and after the sampling. The infants were weighed and measured at local health care centers. Plasma leptin concentration was measured by radio immunoassay (Linco Research, St Charles, MO) using recombinant 125I-leptin as tracer. RESULTS: We found no differences between the group receiving cod liver oil and the group receiving corn oil in any of the measured variables; thus, the groups are treated statistically as one. Leptin concentration in maternal plasma increased during pregnancy from 15.5 +/- 9.0 microg/L (n = 175) in week 18 to 17.7 +/- 10.7 microg/L (n = 166) in week 35. Mothers, pregnant with female fetuses (n = 77), had a significant increase in plasma leptin concentration, from 15.5 +/- 8.8 microg/L (n = 83) at 18 weeks to 18.5 +/- 10.9 microg/L (n = 80) at 35 weeks of pregnancy, whereas in mothers pregnant with male fetuses, the increase was insignificant (15.4 +/- 9.3 microg/L (n = 92) to 17.0 +/- 10.5 microg/L (n = 86). BMI increased during the same time period, from 24.2 +/- 3.3 kg/m to 27.8 +/- 3.8 kg/m (n = 174). There was a significant correlation between BMI and plasma leptin concentration at 18 weeks (r = 0.54, n = 169) and at 35 weeks (r = 0.45, n = 160), but we found no change in the relative leptin concentration (plasma leptin concentration/BMI) from week 18 to week 35. We found no significant difference between smokers and nonsmokers in plasma leptin concentration, neither at 18 nor 35 weeks of pregnancy. Gender differences in plasma leptin concentration was present already at birth in umbilical cord plasma (10.8 +/- 9.2 microg/L for girls [n = 65] vs 7.6 +/- 6.6 microg/L for boys [n = 74]). We also observed gender differences in plasma leptin concentration at 4 weeks (3.9 +/- 1.8 microg/L, n = 68 vs 3.2 +/- 1.8 microg/L, n = 71) and 14 weeks of age (4.9 +/- 2.1 microg/L, n = 61 vs 4.1 +/- 3.1 microg/L, n = 73). Plasma leptin levels at 4 and 14 weeks were lower than the level in umbilical cord plasma (n = 101). An increase in plasma leptin concentration was observed from 4 to 14 weeks of age, both for girls (n = 48) and for boys (n = 60). Leptin concentration in umbilical cord plasma correlated with birth weight (r = 0.44, n = 139), and there was significant corre

Adipose Tissue↗
PubMed1998

Effect of a coffee lipid (cafestol) on cholesterol metabolism in human skin fibroblasts.

Consumption of boiled coffee promotes an elevation of plasma cholesterol concentration in humans. The active compounds found in the lipid fraction of the coffee have been identified as the diterpenes cafestol and kahweol. We have studied the effects of pure cafestol on cholesterol metabolism in human skin fibroblasts (HSF). The uptake of [125I]-labeled tyramine cellobiose-labeled low density lipoprotein ([125I]TC-LDL) was decreased by about 50% (P< 0.05) after 18 h preincubation time with cafestol (20 microg/ml), as compared to the control cells. The specific binding of radiolabeled LDL was reduced by 54% (P < 0.05) after preincubation for 18 h with cafestol. A reduced amount of LDL receptors was demonstrated by a protein-normalized Scatchard plot analysis (20% decrease in Bmax) as well as by immunoblotting (25%) after cafestol incubation. No significant effect was observed on the level of mRNA for the LDL receptor after 11 and 23 h incubation with cafestol. Furthermore, we transfected HSF cells with a promoter region for the LDL receptor gene linked to a reporter gene, chloramphenicol acetyl transferase (CAT). No change was seen in the CAT activity after incubation with cafestol (20 microg/ml). Moreover, cafestol caused a 2.3-fold (P < 0.05) higher incorporation of radiolabeled [14C]oleic acid into cholesteryl esters after 24 h incubation, as compared to control cells, suggesting an increased acyl-CoA:cholesterol acyl transferase (ACAT) activity. Incorporation of [14C]acetate into cholesterol was reduced by approximately 40% (P < 0.05) with cafestol (20 microg/ml), as compared to control after 24 h preincubation, indicating a decreased 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity. Our results suggest that intake of cafestol may cause increased concentration of plasma cholesterol via the down-regulation of low density lipoprotein receptors by post-transcriptional mechanisms.

Acetates↗
PubMed1997

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↗
PubMed1997

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↗