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Low doses of eicosapentaenoic acid, docosahexaenoic acid, and hypolipidemic methylated forms of eicosapentaenoic acid have no effect on lipid peroxidation
Friday, 28 May 1999 Poster presentation: Diet and cardiovascular disease Conclusions: Our trial suggests that the 2week consumption o f to-3 eggs does not provoke plasma cholesterol content. Instead, the intake ofo~-3 eggs tend to produce mild but favourable changes in the lipid profile.
EFFECTS OF NUTRITION PROGRAM ON LIPID PROFILE IN CHILDREN WITH ATHEROSCLEROSIS RISK FACTORS A. Sierakowska-Fijatek, M. Wosik-Erenbek. Department of Pediatrics'.
Milita~ Medical Academy, Lodz. Poland Atherosclerosis and cardiovascular disease are the most important health problems in Poland. It is mainly adult's disease, but atherosclerosis begins in childhood and preventive program should be started in childhood. The aim of our study was to estimate the role of diet in children with atherosclerosis risk factors. The risk level was evaluated and corelated with the nutrition habits and good intake during the last 24 hours. Proposed changes in the nutrition program towards elimination of inproper nutrition habits were investigated in regard children and their parents attitude and the life style. The study comprised children aged 7-15 with atherosclerosis risk factors. Two groups were found: 1/29 children with lipid disturbance and 2/26 children with other risk factors, but without lipid disorders. Results: We showed that nutrition habits have several disturbance: too many energy from total fat inproper ratio of vegetable to animal fats, to low energy in carbohydrates intake. After 10 months dietary preventive we showed positive influence to normalisation the nutrition habits. We had reduction energy from total fat in daily food intake, increase energy from vegetable and carbohydrates. Our researches showed decrease in the lipid level/total cholesterol, LDL-cholesterol, triglicerydes in blood/. Conclusions: Dietary modifications of children and whole family have positive influence on lipid level in investigated groups. LOW DOSES OF EICOSAPENTAENOIC ACID, DOCOSAHEXAENOIC ACID, AND HYPOLIPIDEMIC METHYLATED FORMS OF EICOSAPENTAENOIC ACID HAVE NO EFFECT ON LIPID PEROXIDATION H. Vaagenes. Z.A. Muna, L. Madsen, R.K. Berge. Department of Clinical Biochemisto; UniuersiO' of Bergen, N-5021 Haukeland Hospital, Bergen.
Norway Fish oil, which contains the polyunsaturated fatty acids eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), is beneficial in prevention of several diseases, especially cardiovascular diseases. However, polyunsaturated fatty acids can easily be peroxidized, and it has been claimed that large intake of fish oil can be detrimental. We studied the relationship between hypolipidemic effect and oxidative stress in rats. In this intention we measured plasma lipids, the peroxisomal H202-producing fatty acyI-CoA oxidase (FAO) activity, as well as the content of vitamins E, A and C, thiols, and lipid peroxidation in plasma and liver. High doses of EPA are necessary to cause hypotriglyceridemia, while high doses of DHA have no triglyceridelowering effect. The hypolipidemic effect of EPA was potentiated by branching, and the resulting 2- and 3-methylated EPA-molecules caused hypolipidemic effects at low doses. The most potent hypolipidemic EPAderivative, 2.2-dimethyl EPA, did not change the malondialdehyde content in liver or plasma. Plasma vitamin E decreased only after supplementation of those EPA-derivatives that caused the greatest increase in the FAO activity. The activity of FAO increased after administration of both EPA and DHA at high doses. High doses of EPA and DHA decreased the plasma vitamin E content, while only DHA elevated the lipid peroxidation. In conclusion, increased peroxisomal IS-oxidation in combination with high amounts of polyunsaturated fatty acids caused elevated lipid peroxidation. At low doses of polyunsaturated fatty acids, the lipid peroxidation was unchanged, in spite of increased peroxisomal ~-oxidation, indicating that polyunsaturation is the most important factor for lipid peroxidation. DIETARY MEDIUM-CHAIN TRIACYLGLYCEROL (MCT) INDUCES HYPERCHOLESTEROLEMIA ALTHOUGH PREVENTING THE POST-PRANDIAL RISE OF PLASMA TRIACYLGLYCEROL
131
of corn oil (CO) and MCT added in their low-fat diet along 12 weeks. Subjects were initially on a low fat diet alone (2 wk). In the ensuing 4week period they received CO only. Thereafter, along 2 wk-periods the subjects sequentially fed mixed oil CO:MCT added in their diet in the following proportions: 3:1, I:1 and 0:1. Fasting plasma total cholesterol (TC), triacylglycerol (TAG) and HDL-cholesterol (HDL-C) concentrations were measured at the end of each period. At the end of the 100% CO and 100% MCT periods subjects were submitted to a test meal, containing slim milk, sucrose and their respective oil (40 g fat/m2 body surface) that had been added in their daily diets; TC and TAG were measured along 8 hours at 2-hour intervals. Their body weight and amount of added dietary fat were stable throughout the whole study. VLDL, IDL, LDL and total HDL were obtained after discontinuos gradient density ultracentrifugation and their contents of TC, TAG, total protein (Pr) and phosfolipids (PL), in addition to apoA-! content of HDL were measured. Fasting concentrations (mmol/L) of TC, TAG, HDL-C, non-HDL-C and the post-prandial (AUC) TAG (mmol/L x h) are shown below: concentration
100%CO
100% MCT
TC TAG HDL-C NON-HDL-C TAG-AUC(test meal}
5.325:0.96 5.295:2.87 1.00::[:0./4 4.525:092 17.945:9.64
6A051.14a 6.2753.20 0.93±0.06 5.375:I.I Ib 5.02+4.87b
ap < 0.05 ¢FriedmanTest};bp < 0.005 (WilcoxonTest) In hypertriglyceridemics, although failing to lower their fasting plasma TAG, MCT has the advantage of preventing the postprandial rise of plasma TAG. In the long run, however, MCT has the disadvantage of raising fasting TC and non-HDL-C plasma concentrations by unknown mechanisms. DIFFERENT METABOLIC AND HYPOLIPIDEMIC PROPERTIES OF EICOSAPENTAENOIC AND DOCOSAHEXAENOIC ACID L. Madsen 1 , A.C. Rustan 2, H. Vaagenes t, E. D y m 1 , R.K. Berge 1.
t Department of Clinical Biochemistry. University of Bergen, Haukeland Hospital. N-5021 Bergen." 2Department of Pharmacology. School of Pharmacy UniuersiO, of Oslo. Norwav Decreased triacylglycerol synthesis within hepatocytes due to decreased 1,2diacylglycerol acyltransferase (DGAT) activity, has been suggested to be an important mechanism by which diets rich in fish oil lower plasma triacylglycerol levels. To contribute to the understanding of the triacylglycerol-lowering mechanism of fish oil, the different metabolic and hypolipidemic properties of EPA and DHA, were studied in cultured rat hepatocytes and isolated rat liver microsomes. Cellular uptake of EPA and DHA was similar at equal concentrations, but EPA was oxidized to a much greater extent that DHA at all concentrations. EPA-CoA was a much poorer substrate than DHA-CoA for DGAT. Moreover, EPA-CoA and not DHA-CoA inhibited esterification of oleoyI-CoA into triacylglycerol. The distribution of [1-14C]palmitie acid was shifted towards oxidation in the presence o f EPA but not DHA or oleic acid. Subsequently, less [1J4C]labeled palmitic acid was incorporated into triacylglycerol in the presence of EPA, than DHA and oleic acid. The present study, strongly support the hypothesis that EPA, and not DHA, lowers plasma triacylglycerol by decreased triacylglycerol synthesis within the hepatoeytes, possible due to decreased DGAT activity and increased mitochondrial fatty acid oxidation. Our data from feeding experiments indeed show that pure EPA, but not pure DHA lower plasma triacylglycerol in rats. However, DHA and not EPA, is the fatty acid responsible for the observed peroxisomal proliferating effect of fish oil. EPA feeding also led to a decrease in hepatic fat droplets whereas DHA, which increased the peroxisomal beta-oxidation, actually increased the volume fraction of hepatic fat droplets. Interestingly, fenofibrate and 3-thia fatty acids seem to operate by the same mechanism as EPA, i.e, by increasing the mitochondrial betaoxidation capacity.
L. Asakura, A.M.R Lottenberg, M.Q.T.S. Neves, V.S. Nunes, E.R. Nakandakare, J.C. Rocha, E.C.R. Quint~o. Lipids Laboratory (LIMIO).
University qf S~o Paulo Medical School, S~o Paulo, Brazil Previous studies have shown divergent results concerning the influence of MCT on lipid and lipoprotein metabolism. We studied 10 primary hypertriglyceridemic subjects (6 women and 4 men) that ate different proportions
71st EAS Congress and Satellite Symposia
EFFECTS OF NUTRITION PROGRAM ON LIPID PROFILE IN CHILDREN WITH ATHEROSCLEROSIS RISK FACTORS A. Sierakowska-Fijatek, M. Wosik-Erenbek. Department of Pediatrics'.
Milita~ Medical Academy, Lodz. Poland Atherosclerosis and cardiovascular disease are the most important health problems in Poland. It is mainly adult's disease, but atherosclerosis begins in childhood and preventive program should be started in childhood. The aim of our study was to estimate the role of diet in children with atherosclerosis risk factors. The risk level was evaluated and corelated with the nutrition habits and good intake during the last 24 hours. Proposed changes in the nutrition program towards elimination of inproper nutrition habits were investigated in regard children and their parents attitude and the life style. The study comprised children aged 7-15 with atherosclerosis risk factors. Two groups were found: 1/29 children with lipid disturbance and 2/26 children with other risk factors, but without lipid disorders. Results: We showed that nutrition habits have several disturbance: too many energy from total fat inproper ratio of vegetable to animal fats, to low energy in carbohydrates intake. After 10 months dietary preventive we showed positive influence to normalisation the nutrition habits. We had reduction energy from total fat in daily food intake, increase energy from vegetable and carbohydrates. Our researches showed decrease in the lipid level/total cholesterol, LDL-cholesterol, triglicerydes in blood/. Conclusions: Dietary modifications of children and whole family have positive influence on lipid level in investigated groups. LOW DOSES OF EICOSAPENTAENOIC ACID, DOCOSAHEXAENOIC ACID, AND HYPOLIPIDEMIC METHYLATED FORMS OF EICOSAPENTAENOIC ACID HAVE NO EFFECT ON LIPID PEROXIDATION H. Vaagenes. Z.A. Muna, L. Madsen, R.K. Berge. Department of Clinical Biochemisto; UniuersiO' of Bergen, N-5021 Haukeland Hospital, Bergen.
Norway Fish oil, which contains the polyunsaturated fatty acids eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), is beneficial in prevention of several diseases, especially cardiovascular diseases. However, polyunsaturated fatty acids can easily be peroxidized, and it has been claimed that large intake of fish oil can be detrimental. We studied the relationship between hypolipidemic effect and oxidative stress in rats. In this intention we measured plasma lipids, the peroxisomal H202-producing fatty acyI-CoA oxidase (FAO) activity, as well as the content of vitamins E, A and C, thiols, and lipid peroxidation in plasma and liver. High doses of EPA are necessary to cause hypotriglyceridemia, while high doses of DHA have no triglyceridelowering effect. The hypolipidemic effect of EPA was potentiated by branching, and the resulting 2- and 3-methylated EPA-molecules caused hypolipidemic effects at low doses. The most potent hypolipidemic EPAderivative, 2.2-dimethyl EPA, did not change the malondialdehyde content in liver or plasma. Plasma vitamin E decreased only after supplementation of those EPA-derivatives that caused the greatest increase in the FAO activity. The activity of FAO increased after administration of both EPA and DHA at high doses. High doses of EPA and DHA decreased the plasma vitamin E content, while only DHA elevated the lipid peroxidation. In conclusion, increased peroxisomal IS-oxidation in combination with high amounts of polyunsaturated fatty acids caused elevated lipid peroxidation. At low doses of polyunsaturated fatty acids, the lipid peroxidation was unchanged, in spite of increased peroxisomal ~-oxidation, indicating that polyunsaturation is the most important factor for lipid peroxidation. DIETARY MEDIUM-CHAIN TRIACYLGLYCEROL (MCT) INDUCES HYPERCHOLESTEROLEMIA ALTHOUGH PREVENTING THE POST-PRANDIAL RISE OF PLASMA TRIACYLGLYCEROL
131
of corn oil (CO) and MCT added in their low-fat diet along 12 weeks. Subjects were initially on a low fat diet alone (2 wk). In the ensuing 4week period they received CO only. Thereafter, along 2 wk-periods the subjects sequentially fed mixed oil CO:MCT added in their diet in the following proportions: 3:1, I:1 and 0:1. Fasting plasma total cholesterol (TC), triacylglycerol (TAG) and HDL-cholesterol (HDL-C) concentrations were measured at the end of each period. At the end of the 100% CO and 100% MCT periods subjects were submitted to a test meal, containing slim milk, sucrose and their respective oil (40 g fat/m2 body surface) that had been added in their daily diets; TC and TAG were measured along 8 hours at 2-hour intervals. Their body weight and amount of added dietary fat were stable throughout the whole study. VLDL, IDL, LDL and total HDL were obtained after discontinuos gradient density ultracentrifugation and their contents of TC, TAG, total protein (Pr) and phosfolipids (PL), in addition to apoA-! content of HDL were measured. Fasting concentrations (mmol/L) of TC, TAG, HDL-C, non-HDL-C and the post-prandial (AUC) TAG (mmol/L x h) are shown below: concentration
100%CO
100% MCT
TC TAG HDL-C NON-HDL-C TAG-AUC(test meal}
5.325:0.96 5.295:2.87 1.00::[:0./4 4.525:092 17.945:9.64
6A051.14a 6.2753.20 0.93±0.06 5.375:I.I Ib 5.02+4.87b
ap < 0.05 ¢FriedmanTest};bp < 0.005 (WilcoxonTest) In hypertriglyceridemics, although failing to lower their fasting plasma TAG, MCT has the advantage of preventing the postprandial rise of plasma TAG. In the long run, however, MCT has the disadvantage of raising fasting TC and non-HDL-C plasma concentrations by unknown mechanisms. DIFFERENT METABOLIC AND HYPOLIPIDEMIC PROPERTIES OF EICOSAPENTAENOIC AND DOCOSAHEXAENOIC ACID L. Madsen 1 , A.C. Rustan 2, H. Vaagenes t, E. D y m 1 , R.K. Berge 1.
t Department of Clinical Biochemistry. University of Bergen, Haukeland Hospital. N-5021 Bergen." 2Department of Pharmacology. School of Pharmacy UniuersiO, of Oslo. Norwav Decreased triacylglycerol synthesis within hepatocytes due to decreased 1,2diacylglycerol acyltransferase (DGAT) activity, has been suggested to be an important mechanism by which diets rich in fish oil lower plasma triacylglycerol levels. To contribute to the understanding of the triacylglycerol-lowering mechanism of fish oil, the different metabolic and hypolipidemic properties of EPA and DHA, were studied in cultured rat hepatocytes and isolated rat liver microsomes. Cellular uptake of EPA and DHA was similar at equal concentrations, but EPA was oxidized to a much greater extent that DHA at all concentrations. EPA-CoA was a much poorer substrate than DHA-CoA for DGAT. Moreover, EPA-CoA and not DHA-CoA inhibited esterification of oleoyI-CoA into triacylglycerol. The distribution of [1-14C]palmitie acid was shifted towards oxidation in the presence o f EPA but not DHA or oleic acid. Subsequently, less [1J4C]labeled palmitic acid was incorporated into triacylglycerol in the presence of EPA, than DHA and oleic acid. The present study, strongly support the hypothesis that EPA, and not DHA, lowers plasma triacylglycerol by decreased triacylglycerol synthesis within the hepatoeytes, possible due to decreased DGAT activity and increased mitochondrial fatty acid oxidation. Our data from feeding experiments indeed show that pure EPA, but not pure DHA lower plasma triacylglycerol in rats. However, DHA and not EPA, is the fatty acid responsible for the observed peroxisomal proliferating effect of fish oil. EPA feeding also led to a decrease in hepatic fat droplets whereas DHA, which increased the peroxisomal beta-oxidation, actually increased the volume fraction of hepatic fat droplets. Interestingly, fenofibrate and 3-thia fatty acids seem to operate by the same mechanism as EPA, i.e, by increasing the mitochondrial betaoxidation capacity.
L. Asakura, A.M.R Lottenberg, M.Q.T.S. Neves, V.S. Nunes, E.R. Nakandakare, J.C. Rocha, E.C.R. Quint~o. Lipids Laboratory (LIMIO).
University qf S~o Paulo Medical School, S~o Paulo, Brazil Previous studies have shown divergent results concerning the influence of MCT on lipid and lipoprotein metabolism. We studied 10 primary hypertriglyceridemic subjects (6 women and 4 men) that ate different proportions
71st EAS Congress and Satellite Symposia