Oxidized fatty acids promote atherosclerosis only in the presence of dietary cholesterol in low-density lipoprotein receptor knockout mice

Studies suggest that heated oils contribute to the presence of oxidized components in the circulating lipoproteins and to the development of atherosclerosis in animals. We evaluated the effects of 11-13 wk of consumption of a well defined dietary oxidized fatty acid, 13-hydroxylinoleic acid (13-HODE) (8 mg), on atherosclerotic lesion development and plasma cholesterol concentrations in mice fed diets varying in fat and cholesterol contents. LDL receptor knockout mice were used in two feeding studies. In study 1, oxidized fatty acid consumption in association with a high fat diet increased aortic lesion areas by >100% (P < 0.05). Surprisingly, oxidized fatty acid intake also tended to increase plasma total cholesterol (P = 0.12) and LDL cholesterol (P < 0.05) as well as oxidative stress as measured by higher levels of autoantibodies to oxidatively modified proteins (P = 0.008). However, in mice fed a nonpurified diet, oxidized fatty acids were not atherogenic and may even have been beneficial, as indicated by a lower plasma triglyceride (TG) concentration (P < 0.05). In study 2, mice were fed either a high fat, medium fat or low fat diet to evaluate whether the increase in aortic lesions due to oxidized fatty acid consumption in study 1 was a result of the associated higher plasma total and LDL cholesterol concentrations. In study 2, 13-HODE-treated mice in the medium and low fat diet groups but not those fed the high fat diet had larger atherosclerotic lesions (P < 0.05). Additionally, plasma total and LDL cholesterol as well as TG were not affected by HODE treatment. However, the total cholesterol:HDL cholesterol ratio was higher in treated mice (P < 0.05) and HDL cholesterol was lower in HODE-treated mice that were fed the low fat diet (P < 0.05). Our results suggest that, in mice fed cholesterol, oxidized fatty acids may be atherogenic, both in terms of increased oxidative stress (as seen in study 1) and by increasing the atherogenicity of the plasma cholesterol profile.     

脂肪酸对糖尿病模型大鼠血磷脂脂肪谱的影响

目的　观察富含n - 6和n - 3多不饱和脂肪酸 (PUFA)饲料对自发性 2型糖尿病模型OtsukaLong -E vansTokushimaFatty(OLETF)大鼠糖代谢及血清磷脂 (S -PL)中脂肪酸 (FA)组成的影响。 方法　将 2 0只 14周龄雄性OLETF大鼠随机分为 2组。两组大鼠饲料总能量相同 ,其中饱和脂肪酸 (SFA)、单不饱和脂肪酸 (MUFA)和PU FA的百分含量亦相同 ,但分别富含n - 6PUFA〔4 1 6mol/ (10 0mol·脂肪 )〕和n - 3PUFA〔2 0 4mol/ (10 0mol·脂肪 )〕 ,饮食干预 10周。第 2 4周时实施口服糖耐量试验 (OGTT)、胰岛素水平测定和S -PL中FA组成测定。结果　干预期间 ,两组大鼠总进食量及体重增长无显著性差异 ;干预后OGTT及胰岛素水平测定表明 ,n - 3组相对于n - 6组具有较好的胰岛素敏感性。n - 3组大鼠S -PL中 18∶1(n - 9)、MUFA总量、18∶2 (n - 6 )、各n - 3系PUPA百分含量较n- 6组高 ,n - 6PUFA总量、2 0∶4 (n - 6 )百分含量较低。结论　n - 3PUFA的摄入相对于n - 6PUFA对OLETF大鼠的糖代谢有益 ,OLETF大鼠S -PL的FA组成受到饲料中FA的影响 ,但并不是其直接反应。     

Effects of dietary fatty acid composition on macronutrient selection and synaptosomal fatty acid composition in rats

Our previous work showed that rats consuming 20% (wt/wt) lard diets selected more protein and less carbohydrate than did rats fed 20% (wt/wt) soybean oil diets. To determine if this effect is specific to saturated fat source and to measure changes in fatty acid composition of synaptosomal phospholipids, male Wistar rats were fed a 20% (wt/wt) soybean oil or tallow diet with 24% protein and 48% carbohydrate for 2 wk. Rats then self-selected from two diets with the same fat previously fed but different protein and carbohydrate composition (5% protein, 67% carbohydrate and 55% protein, 17% carbohydrate). Tallow-fed rats selected more protein and less carbohydrate than did soybean oil-fed rats. Dietary fat also affected fatty acid composition of synaptosomal phospholipids, phosphatidylcholine being most affected and phosphatidylinositol most resistant. Later studies determined if selection differences were due to taste. When rats self-selected without prior exposure to diets, tallow-fed rats selected more protein and less carbohydrate than did soybean oil-fed rats during the last 2 wk but not the first 2 wk. When rats selected from diets with identical protein and carbohydrate composition but different dietary fat, rats consumed slightly greater amounts of the tallow diet at each protein level. The relative intake of tallow and soybean oil diets, however, did not vary significantly with dietary protein treatment. These results confirm that rats fed saturated fat diets select more protein and less carbohydrate than do rats fed polyunsaturated fat diets and suggest this difference is not due to taste factors.     

Down-regulation of the low-density lipoprotein receptor by dietary cholesterol

To determine the effect of dietary cholesterol on the low-density lipoprotein (LDL) receptor of circulating mononuclear cells, nine adults (six men, three women) consumed a natural diet consisting of 45% of the calories as carbohydrate, 40% as fat, and 15% as protein, polyunsaturated/saturated fatty acid ratio 0.80 to 0.84, and either 137 +/- 25 mg cholesterol per day (low cholesterol phase) or 1034 +/- 25 mg cholesterol per day (high cholesterol phase). The study lasted 2 months with 1 month in each phase and used a cross-over design. The levels of plasma triglyceride, plasma cholesterol, very low-density and high-density lipoprotein cholesterol, and apolipoproteins B, A-I, and A-II were similar in the two diet phases. The high cholesterol diet was associated with an 11 +/- 9% increase (p less than 0.02) in LDL cholesterol level and a 41 +/- 14% decrease in LDL receptor activity (p less than 0.05, n = 6). The percentage decrease in LDL receptor activity correlated with the percentage increase in LDL cholesterol (r = -0.796, p = 0.06, n = 6). Thus, high levels of dietary cholesterol can down-regulate the LDL receptor in humans.     

饮食n-3脂肪酸对小鼠脑脂类中多不饱和脂肪酸构成的影响

【目的】观察饮食鱼油n-3多不饱和脂肪酸(n-3 PUFAs)对脑内不同脂类中PUFAs构成的影响。【方法】使用C57BL/6J雌性小鼠,在胎儿期和幼年期分别给予不同种类高脂饲料(18%脂肪,供能比为36%)喂养-高脂豆油饲料、高脂鱼油饲料和高脂豆油:鱼油(5∶1)混合饲料,以正常饲料(6%脂肪来自豆油,供能比为12%)为对照,时间为4个月。采用薄层层析分离脑组织中各主要脂类成份,然后采用甲酯化-气相色谱分析对各脂类成份中的脂肪酸进行测定。【结果】鱼油饲料喂养改变了小鼠脑内主要脂类中PUFAs的构成。在磷脂中,虽然5种PUFAs在各饲料组之间差异均无显著性(P>0.05),但二十二碳六烯酸(DHA)/花生四烯酸(AA)(1.94±0.41)以及n-3/n-6 PUFAs比值(2.31±0.75)在鱼油组较其它三组显著升高(P<0.05);在甘油一和二酯中,与豆油组相比,鱼油组和豆油:鱼油混合组LA含量(0.31±0.09%,0.65±0.58%)降低,而鱼油组DHA/AA(2.60±1.66)以及n-3/n-6 PUFAs比值(2.31±0.75)升高(P<0.05);在甘油三酯中,与豆油组相比,鱼油组和豆油:鱼油混合组AA含量(1.62±0.53%,1.12±0.36%)和EPA含量(0.98±0.58%,1.34±0.31%)显著降低,而DHA/AA比值(1.14±0.21,1.46±0.58)升高(P<0.05),但DHA含量在三组之间无差异(P>0.05);在游离脂肪酸中,5种PUFAs在各饲料组之间无差异(P>0.05)。【结论】饮食鱼油n-3 PUFAs摄入增多虽然不影响脑内DHA的聚积,但改变了DHA/AA以及n-3/n-6PUFAs的比值。甘油酯类可能是脑摄取、聚积DHA的主要直接来源之一。     

Effect of dietary fatty acids on the postprandial fatty acid composition of triacylglycerol-rich lipoproteins in healthy male subjects

OBJECTIVE: The aim of the present study was to investigate the effect of trans-18:1 isomers compared to other fatty acids, especially saturates, on the postprandial fatty acid composition of triacylglycerols (TAG) in chylomicrons and VLDL. DESIGN: A randomised crossover experiment where five interesterified test fats with equal amounts of palmitic acid (P fat), stearic acid (S fat), trans-18:1 isomers (T fat), oleic acid (O fat), or linoleic acid (L fat) were tested. SUBJECTS: A total of 16 healthy, normolipidaemic males (age 23+/-2 y) were recruited. INTERVENTIONS: The participants ingested fat-rich test meals (1 g fat per kg body weight) and the fatty acid profiles of chylomicron and VLDL TAG were followed for 8 h. RESULTS: The postprandial fatty acid composition of chylomicron TAG resembled that of the ingested fats. The fatty acids in chylomicron TAG were randomly distributed among the three positions in accordance with the distributions in test fats. Calculations of postprandial TAG concentrations from fatty acid data revealed increasing amounts up to 4 h but lower response curves (IAUC) for the two saturated fats in accordance with previous published data. The T fat gave results comparable to the O and L fats. The test fatty acids were much less reflected in VLDL TAG and there was no dietary influence on the response curves. CONCLUSIONS: The fatty acid composition in the test fats as well as the positional distributions of these were maintained in the chylomicrons. No specific clearing of chylomicron TAG was observed in relation to time.     

Evaluation of the composition of omega-3 fatty acids in dietary oil supplements

Aim: The aim of the present study was to determine the fatty acid composition of 19 dietary oil supplements that are commercially available in Australia, comparing findings with manufacturers' reported omega-3 fatty acid content. Methods: Fifteen fish oil supplements and four non-fish oil supplements were obtained from Australian retail stores. Fatty acids were derivatised, and fatty acid methyl esters were quantitated using classical GC-flame ionisation detection methods. Composition of eicosapentaenoic acid and docosahexaenoic acid reported by supplement manufacturers was compared with experimental values using the Bland-Altman plot. Results: The combined eicosapentaenoic acid and docosahexaenoic acid content in the fish oil and non-fish oil supplements was 17.63–71.45% and 0.00–0.05% respectively. A high level of congruency was observed for the composition of eicosapentaenoic acid and docosahexaenoic acid reported by manufacturers and determined experimentally (mean difference, eicosapentaenoic acid, 13.2 mg; docosahexaenoic acid, 12.8 mg). Conclusion: Current practice in pre-market assessment of complementary medicines in Australia is satisfactory for supplements examined in the present study. Intake of these fish oil supplements can be used to provide high levels of long-chain omega-3 fatty acids that would be otherwise difficult to achieve through normal dietary intake alone.     

Will dietary omega-3 fatty acids change the composition of human milk?

The most abundant long-chain polyunsaturated fatty acid in brain and retinal lipids is docosahexaenoic acid (DHA, C22:6 omega 3). It becomes incorporated into nerve tissues mostly in utero and during the 1st yr of life. DHA is derived in humans either performed in the diet or by hepatic synthesis from dietary linolenic acid (C18:3 omega 3). Since human milk contains DHA, this study was designed to see if increased dietary DHA would be reflected in a higher DHA content in human milk. Eight lactating women were given supplements of a fish oil concentrate rich in omega-3 fatty acids, including DHA (11% of fatty acids). Six women took 5 g/day of fish oil for 28 days; five women consumed 10 g/day for 14 days; and one woman consumed 47 g/day for 8 days. Each intake level of fish oil produced significant dose-dependent increases in the DHA content of milk and plasma. Base-line DHA levels in milk were 0.1 +/- 0.06% of total fatty acids. Five g/day of fish oil raised the levels to 0.5 +/- 0.1% (p less than 0.001); 10 g/day raised DHA levels to 0.8 +/- 0.1% (p less than 0.001); and 47 g/day produced DHA levels of 4.8%. The results of this study indicated that relatively low intakes of dietary DHA significantly elevated milk DHA content. This would clearly elevate the infant's DHA intake and might have implications for brain and retinal development.     

Effects of dietary n-3 polyunsaturated fatty acids, breed and dietary vitamin E on the fatty acids of lamb muscle, liver and adipose tissue

The effect of feeding n-3 PUFA on the fatty acid composition of muscle, adipose tissue and liver of lambs was investigated. Groups of eight ram lambs per breed, SuffolkxLleyn (24 kg live weight) and Scottish Blackface (18 kg live weight), were each fed one of six diets containing one of three fat sources (50 g fatty acids/kg DM; Megalac((R)) (calcium soap of palm fatty acid distillate; Volac Ltd, Royston, Herts., UK) and formaldehyde-treated whole linseed (Trouw Nutrition UK, Northwich, Ches., UK) either alone or with fish oil (1:1, w/w) and either 100 or 500 mg alpha-tocopheryl acetate/kg DM. Feed was offered ad libitum until slaughter at approximately half breed mature live weight. The type of dietary fat had no effect on intake, growth rate or feed conversion ratio. The 3.0-fold higher concentration of 18 : 3n-3 in the linseed compared with the Megalac((R)) diet approximately doubled (P<0.001) the concentration in the neutral and polar lipid fractions of musculus semimembranosus and liver, and in adipose tissue it increased 2.5-fold. Feeding protected linseed also increased (P<0.001) concentrations of 20 : 5n-3 and 22 : 5n-3 in muscle polar lipids and both lipid fractions of liver. The linseed-fish oil raised the 20 : 5n-3 concentrations above those for the linseed diet and also increased 22 : 6n-3. Scottish Blackface lambs had lower concentrations of 18 : 3n-3 in all lipids compared with Suffolk x Lleyn lambs, but more 20 : 5n-3 in the polar lipids of muscle and liver. High levels of dietary vitamin E were associated with small decreases in the concentration of monounsaturated fatty acids and increases in PUFA. Linseed raised the PUFA : saturated fatty acid ratios in liver and adipose tissue but not in muscle, and improved the n-6 : n-3 fatty acid ratio, as did the linseed-fish oil. Different combinations of dietary fatty acids and better protection against rumen biohydrogenation are required to improve muscle PUFA : saturated fatty acids ratios.     

Effect of dietary n-3 fatty acids on the composition of long- and very-long-chain polyenoic fatty acid in rat retina

The effect of dietary supplementation with n-3 fatty acids, primarily docosahexaenoic acid (DHA) with high purity, on the fatty acid composition, especially very-long-chain fatty acids (VLCFA) longer than DHA, with four or six double bonds, in the rod outer segment (ROS) membranes of young Sprague-Dawley rats was investigated. After several weeks of feeding, diets high in n-3 fatty acids increased the DHA level significantly, while there were decreased levels of most n-6 fatty acids, such as arachidonic acid and 22:5n-6. Six kinds of VLCFA were detected by gas chromatography-mass spectrometry (GC-MS). Feeding a high n-3 fatty acid diet significantly increased the content of some n-3 VLCFAs such as 26:4n-3 and 30:4n-3 in ROS membranes, but not all detected n-3 VLCFAs. This study demonstrates that the dietary level of n-3 fatty acids not only affects the level of DHA, but also the levels of VLCFA in ROS membranes.     

Effect of dietary selenium and omega-3 fatty acids on muscle composition and quality in broilers

Background  

Human health may be improved if dietary intakes of selenium and omega-3 fatty acids are increased. Consumption of broiler meat is increasing, and the meat content of selenium and omega-3 fatty acids are affected by the composition of broiler feed. A two-way analyses of variance was used to study the effect of feed containing omega-3 rich plant oils and selenium enriched yeast on broiler meat composition, antioxidation- and sensory parameters. Four different wheat-based dietary treatments supplemented with 5% rapeseed oil or 4% rapeseed oil plus 1% linseed oil, and either 0.50 mg selenium or 0.84 mg selenium (organic form) per kg diet was fed to newly hatched broilers for 22 days.     

Effects of dietary fatty acids and exercise on body-weight regulation and metabolism in rats

OBJECTIVE: To assess the interaction of high-fat diets (HF) made with different dietary fatty acids and exercise on body-weight regulation, adiposity, and metabolism. RESEARCH METHODS AND PROCEDURES: Male Wistar rats born to dams fed HF diets (40% w/w) made with either fish oil (FO), soybean oil (SO), or palm oil (PO) were fed diets similar to their dams and divided randomly into exercise (EX, swimming) or sedentary control (SD) groups when they were 9 weeks old. EX lasted for 6 weeks. Twenty-four hours after the last EX bout, fasted rats were killed by decapitation. Chemical analyses and body composition analysis were conducted. RESULTS: The results demonstrated that different fatty acids had different effects on body weight, composition, and metabolism. SO-fed rats gained the most weight and fat. EX reduced body weight of FO- and PO-fed rats, but SO-fed rats were still heavier and fatter than other rats. Data from SO- and PO-fed rats suggested that they are insulin resistant and that EX normalized this abnormality. Of the three HF diets used, FO produced the least adverse effects compared with PO and SO. DISCUSSION: Not only the quantity of dietary fat, but also the type of fat used, will produce different effects on body weight and metabolism. EX ameliorates the suggested insulin resistance induced in rats fed either highly saturated or n-6 polyunsaturated fatty acids. Long-chain n-3 polyunsaturated fatty acids, as found in fish oil, are more beneficial than n-6 polyunsaturated fatty acids when fed in high amounts to rats.     

Effect of palm oil on plasma lipoprotein concentrations and plasma low-density lipoprotein composition in non-human primates

Palm oil (PO) contains ~43% of palmitic acid. It is the most abundant saturated fatty acid in the diet and it is generally considered the primary cholesterol (C)-raising fatty acid. However, the effect of palmitic acid on plasma cholesterol appears to depend on the cholesterol content of the diet. The aim of this study was to determine the effect of PO with either a high-fat, high-C or moderate-fat, moderate-C diet on lipoprotein C and low-density lipoprotein (LDL) composition. Fifty adult, male vervet monkeys were randomly assigned to the high-fat diet group (HFD: 35%E fat, ~0.106 mg C/kJ; n =20) and the moderate-fat diet group (MFD: 30%E fat, ~0.027 mg C/kJ; n =30). Baseline LDL-C, high-density lipoprotein (HDL)-C and body weight were used to stratify the vervets into comparable experimental groups within each dietary group. The HFD group was divided into two groups of 10 each: one group continued with the HFD in which 8.1%E was derived from lard (AF); in the other group, AF was substituted isocalorically with PO. The MFD group was divided into three groups of 10 each: one group continued with the MFD in which 11.8%E was derived from AF; in the other two groups, the AF was substituted isocalorically with either sunflower oil (SO) or PO. This article presents preliminary results on plasma lipoproteins and LDL composition after 6 months of dietary intervention. Plasma total and LDL-C was higher in all the groups, but the mean changes elicited by PO with either the HFD or MFD were no different from that observed with AF and SO. There was no difference in the mean change of LDL molecular weight within the HFD and MFD. It is concluded that PO is no different from AF (HFD and MFD) or SO (MFD) in its cholesterolaemic effect.     

Effect of 6 dietary fatty acids on the postprandial lipid profile, plasma fatty acids, lipoprotein lipase, and cholesterol ester transfer activities in healthy young men

BACKGROUND: There is increasing evidence that postprandial triacylglycerol-rich lipoproteins may be related to atherogenic risk. OBJECTIVE: The objective was to investigate the effect of individual fatty acid intakes on postprandial plasma lipoprotein triacylglycerol and cholesterol concentrations, plasma fatty acids, and preheparin lipoprotein lipase and cholesterol ester transfer protein (CETP) activities. DESIGN: Six test fats high (approximately 43% by wt) in stearic acid, palmitic acid, palmitic + myristic acid, oleic acid, elaidic acid (trans 18:1), and linoleic acid were produced by interesterification. After having fasted for 12 h, 16 healthy young men were served the individual test fats incorporated into meals (1 g fat/kg body wt) in random order on different days separated by washout periods. Blood samples were drawn before and 2, 4, 6, and 8 h after the meals. RESULTS: Different responses to the test-fat meals were observed for plasma lipoprotein triacylglycerol and cholesterol concentrations, plasma fatty acid concentrations, and lipoprotein lipase and CETP activities (diet x time interaction: 0.001 < P < 0.05). Intake of the long-chain saturated fatty acids stearic and palmitic acids resulted in a relatively lower lipemic response than did intake of the unsaturated fatty acids, probably because the saturated fatty acids were absorbed less and at a lower rate; therefore, the lipemic response took longer to return to postabsorptive values. CONCLUSIONS: Fatty acid chain length and degree of saturation appear to affect the extent and duration of lipemia and affect hepatic output indirectly. These effects may not be mediated via effects on lipoprotein lipase and CETP activities.     

Effects of dietary trans fatty acids on blood pressure in normotensive subjects.

Consumption of essential fatty acids of the (n-6) series may affect blood pressure in man. Trans fatty acids in the diet interfere with the metabolism of essential fatty acids in rats. We therefore measured the effect of dietary trans fatty acids on blood pressure in 25 men and 34 women. Each subject consumed, in random order, three mixed natural diets, each for three weeks. The composition of the three diets was similar, except for 10.4 per cent of energy, which was provided by either oleic acid, trans fatty acids, or saturated fatty acids. The intake from polyunsaturated fatty acids was 3.4 per cent on the saturated-fat diet and 4.6 per cent on the other two diets. On the oleic-acid diet systolic blood pressure was 113 +/- 12.8 mmHg and diastolic blood pressure 66 +/- 8.3 mmHg, on the trans-fatty-acid diet 112 +/- 12.2 mmHg and 67 +/- 8.1 mmHg, and on the saturated-fat diet 112 +/- 12.6 mmHg and 67 +/- 8.1 mmHg. No significant differences were observed in blood pressure levels between the three diets. We conclude that neither trans nor saturated fatty acids influence blood pressure levels in normotensive subjects relative to oleic acid.     

Effect of ingestion of virgin olive oil on human low-density lipoprotein composition

OBJECTIVE: To measure the incorporation of oleic acid and antioxidants (phenols and vitamin E) to low density lipoprotein (LDL) after acute and short-term ingestion of virgin olive oil. To study whether this incorporation contributes to an increase in LDL resistance to oxidation. SETTING: Department of Food and Nutrition, University of Barcelona, Spain and Department of Lipids and Cardiovascular Epidemiology, IMIM, Barcelona, Spain. SUBJECTS: Sixteen healthy volunteers aged 25-65 y. DESIGN AND INTERVENTIONS: To observe the change in the fatty acid profile, vitamin E, phenolic compounds and LDL oxidation-related variables after the postprandial phase and after daily ingestion of olive oil for one week. RESULTS: Few changes were observed in the postprandial phase. However, after a week of olive oil consumption there was an increase in oleic acid (P=0.015), vitamin E (P=0.047), phenolics (P=0.021) and lag time (P=0.000), and a decrease in the maximum amount of dienes (P=0.045) and oxidation rate (P=0.05). CONCLUSION: After ingestion of virgin olive oil, an increase in antioxidants and oleic acid in LDL was observed as well as an improvement of LDL resistance to oxidation. Our results support the idea that daily ingestion of virgin olive oil could protect LDL from oxidation. SPONSORSHIP: This study was supported by a research grant from Spain (ALI 97-1607-C02-02).