Dietary fatty acid composition in pregnancy alters neurite membrane fatty acids and dopamine in newborn rat brain

The importance of maternal dietary fatty acids on arachidonic acid [AA; 20:4(n-6)] and docosahexaenoic acid [DHA; 22:6(n-3)] in fetal brain nerve growth cone membranes and monoaminergic neurotransmitters was investigated. Rats were fed purified diets containing 20 g/100 g safflower oil with 74.3% 18:2(n-6), 0.2% 18:3(n-3), soybean oil with 55.4% 18:2(n-6), 7.7% 18:3(n-3) or high fish oil with 24.6% 22:6(n-3) through gestation. Tissue for rats within a litter were pooled at birth, brain growth cone membranes prepared and phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) fatty acids quantified by gas-liquid chromatography. Dopamine, serotonin, and the metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid, and 5-hydroxyindolacetic acid were quantified by HPLC. Growth cone membranes from offspring of rats fed safflower oil had significantly lower, and offspring of rats fed high 22:6(n-3) fish oil had significantly higher 22:6(n-3) in PE, PS and PI than the soybean oil group. The growth cone membrane PC, PE and PS 20:4(n-6) was significantly lower in the fish oil than in the soybean or safflower oil groups. Serotonin concentration was significantly higher in brain of offspring in the safflower oil compared with the soybean oil group. The newborn brain dopamine was inversely related to PE DHA and PS DHA (P < 0.001), but positively related to PC AA (P < 0.05). These studies show that maternal dietary fatty acids may alter fetal brain growth cone (n-6) and (n-3) fatty acids, and neurotransmitters involved in neurite extension, target finding and synaptogenesis. The functional importance, however, is not known at this time.     

Effects of n-3 polyunsaturated fatty acids on coronary heart disease

The purpose of this paper is to discuss the role of n-6 and n-3 polyunsaturated fatty acids in coronary heart disease (CHD). The level of n-6 and n-3 fatty acids in plasma and cardiac phospholipids was examined in relation to CHD in man. The fatty acid profile of cardiac phospholipids was also examined in relation to various risk factors of CHD, such as the composition of dietary fat, aging and stress. Life expectancy in Iceland is higher than in other Nordic countries, and the cardiovascular diseases mortality is lower in Iceland in the older age groups. There is a positive correlation between the level of arachidonic acid (AA) in plasma phospholipids (PL) in the normal population and cardiovascular disease mortality in Nordic countries. The level of AA in plasma PL is significantly higher in patients with CHD than in normal subjects. Dietary intake of fish or fish oil lowers cellular levels of AA and favorably influences eicosanoid metabolism in platelets and leukocytes. The roles of n-6 and n-3 fatty acids in heart muscle are less well understood. Rats fed diets containing either 10% butter, corn oil or cod liver oil showed markedly different fatty acid composition of individual phospholipids in sarcolemma. Dietary cod liver oil lowered the AA level in sarcolemmal phosphatidyl choline (PC) and phosphatidyl ethanolamine (PE) by 50% compared to butter or corn oil fed rats, replacing AA with docosahexaenoic acid (DHA). Adaptation to moderate to severe stress induced by repeated administration of catecholamines for 15 days resulted in marked but reversible alterations in the fatty acid profile of cardiac phospholipids. During severe stress the level of AA increased by 50% in PC replacing linoleic acid (LA), whereas in PE the DHA increased markedly replacing LA. Aging was accompanied by similar alterations in cardiac phospholipids, increased levels of AA in PC and increased DHA in PE. The incidence of ventricular fibrillation (VF) and sudden cardiac death induced by isoproterenol in adult rats fed different dietary fat was lowest in rats fed cod liver oil, with a low ratio of AA/DHA in cardiac phospholipids. Mortality due to VF was highest in rats fed corn oil with the highest ratio of AA/DHA. Sudden cardiac death in man was frequently associated with a higher ratio of AA/DHA than observed in people of the same age who died in accidents. The balance between n-6 and n-3 fatty acids in cellular phospholipids seems to play an important role in stress tolerance and survival.     

Dietary fatty acids and inflammation

Introduction:  It is commonly believed that inflammation can be reduced by lowering the dietary ratio of n-6 (linoleic acid) to n-3 polyunsaturated fatty acids as a means of lowering arachidonic acid levels in cell membranes. This review will examine this proposition.
Results:  Although many pro-inflammatory molecules can be produced from arachidonic acid and this long-chain n-6 fatty acid can be produced from linoleic acid, changing dietary linoleic acid intake over a wide range does not have any significant effect on arachidonic acid levels in cell membranes, inflammation or immune functions. There are no data that show lowering dietary n-6 polyunsaturated fats reduces inflammation. In contrast, arachidonic acid levels in cell membranes and inflammatory parameters are lowered by increasing intakes of long-chain n-3 polyunsaturated fatty acids. Resolvins and protectins, both derivatives of long-chain n-3 fats, also have potential anti-inflammatory activity. In high doses, long-chain n-3 fats may have modest, beneficial effects on inflammation in rheumatoid arthritis. However, many studies have shown no effects of fish oil on inflammation parameters.
Conclusions:  The dietary n-6/n-3 ratio is not a useful measure of the inflammatory nature of a diet, though the absolute amount of dietary long-chain n-3 polyunsaturated fatty acids may be a guide.     

Are the n-3 fatty acids from dietary fish oil deposited in the triglyceride stores of adipose tissue?

Adipose tissue is the chief reservoir of the essential fatty acids (n-3 and n-6). To study the incorporation of the dietary n-3 fatty acids eicosapentaenoic acid (EPA) (20:5) and docosahexaenoic acid (DHA) (22:6), and a unique monounsaturated fatty acid, cetoleic acid (22:1n-11), into adipose tissue, rabbits were fed two different processed fish oils: MaxEPA (high in EPA and DHA; Seven Sea Ltd, Hull, UK) and herring oil (high in cetoleic acid). EPA and DHA increased from 0% of total adipose tissue fatty acid, in the adipose tissue of control rabbits to 2.2% and 4.9%, respectively, in MaxEPA-fed rabbits. The DHA-to-EPA ratio in the adipose tissue was higher than that in the diet, indicating alternative metabolic pathways for EPA. In the adipose tissue of herring-oil-fed rabbits, cetoleic acid increased from 0% to 7.9% of total fatty acids. The deposition of EPA and DHA was 1.8% and 2.8%, respectively. Our data indicated that these unique long-chain unsaturated fatty acids from dietary fish oils were readily incorporated into the fat stores from whence they could be mobilized.     

Ingestion of fish oil or a derived n-3 fatty acid concentrate containing eicosapentaenoic acid (EPA) affects fatty acid compositions of individual phospholipids of rat brain, sciatic nerve and retina

The effect of feeding redfish (Sebastes marinus or mantella) oil or a derived n-3 fatty acid concentrate containing eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the fatty acid compositions of individual phospholipids in selected neural tissues was studied in growing male rats. Control animals were given sunflower oil in the diet for the 5-wk feeding trial. Lipid analyses revealed that EPA (20:5n-3) became significantly enriched in all phospholipid fractions (phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol) in the tissues studied (brain, retina and sciatic nerve) in the two n-3 fatty acid dietary groups relative to controls. Corresponding changes were also found in the 22:5n-3 contents of these tissues, whereas little or no significant elevation in DHA (22:6n-3) was found. In contrast, the percentages by weight of the n-6 fatty acids including 18:2n-6, 20:4n-6 (arachidonic acid, AA), 22:4n-6 and 22:5n-6 were generally lower in the various phospholipids/tissues of the animals given fish oil or the n-3 fatty acid concentrate; the levels of 22:5n-6 and 22:4n-6 were markedly affected in this regard. These results indicate that dietary n-3 fatty acids (as EPA plus DHA) can greatly affect the fatty acid compositions of the various membrane phospholipids in nervous tissues within a relatively short time. These biochemical alterations may be important for functional changes including altered membrane fluidity, cellular responses, ion transport and the biosyntheses of AA- and EPA-derived prostaglandins and leukotrienes.     

不同智力水平人群n-3 PUFAs差异及膳食补充对体内脂肪酸组成的影响研究

【目的】研究高智商(IQ>135)与低智商(IQ<90)学生体内n-6与n-3脂肪酸水平差异,以及补充n-3类多不饱和脂肪酸(polyunsaturated fatty acids,PUFAs)对IQ<90的学生体内脂肪酸组成的影响作用。【方法】整群抽取浙江余姚中等水平乡镇的2所普通小学,通过智力测定筛选出IQ<90以及>135的学生两组,采集静脉血分析其脂肪酸组成。采用随机对照研究方法,将IQ<90的学生进行随机分组,分别给予为期3个月的干预食物(富含n-3 PUFAs)与对照食物,对干预前后的血脂肪酸水平数据进行比较。【结果】智商高低学生体内脂肪酸水平存在明显差异:IQ>135的学生其体内花生四稀酸(arachidonic acid,AA)、二十碳五烯酸(eicosapentaenoic acid,EPA)、二十二碳六烯酸(docosa-hexaenoic acid,DHA)以及n-3 PUFAs水平明显高于IQ<90的学生(P<0.001或<0.05);而亚油酸(linoleic acid,LA)水平以及n-6/n-3 PUFAs比例明显低于IQ<90的学生(P<0.05或<0.01)。同时,在对IQ<90的学生补充富含n-3PUFAs的食物后,其体内脂肪酸组成也发生显著变化,表现为:α-亚麻酸(α-linolenic acid,ALA)、EPA、DHA以及n-3 PU-FAs水平显著提高(P<0.05或<0.001),而n-6/n-3 PUFAs比例明显下降(P<0.001)。【结论】智商高的学生体内AA及DHA水平较高而n-6/n-3 PUFAs比例较低。同时,对智商低的学生补充n-3 PUFAs可以改变其体内的脂肪酸组成,使其更为接近高智商学生体内的脂肪酸组成。     

High levels of the (n-6) fatty acid 4,7,10,13,16-docosapentaenoate in the retinas of rabbits are reduced by feeding dietary fish oil from birth to adult life

High levels of 4,7,10,13,16-docosapentaenoic acid [22:5(n-6)], a fatty acid usually associated with (n-3) fatty acid deficiency, have been reported in the retina of young rabbits. We studied the fatty acid composition of the rabbit retina throughout development, from birth to adult life. We also attempted to modify the fatty acid composition of the retina by the feeding of fish oil, high in docosahexaenoic acid [22:6(n-3), DHA]. Female rabbits were fed either a control or 2% fish oil diet through pregnancy and the nursing period. Weaned rabbits received the mothers' diet. In the retinas of control rabbits, 22:5(n-6) represented 3.7% of total fatty acids at birth, reached 15.1% at 9 wk and declined to 5.6% in adult rabbits. However, 22:6(n-3) increased steadily from birth onwards, from 3.8% of total fatty acids at birth to 19.6% in adults. Dietary fish oil increased the trace concentrations of long-chain (n-3) fatty acids in the milk to 10% of total fatty acids, reduced retinal 22:5(n-6) to less than or equal to 0.5% at all ages, and increased DHA to approximately 30% by 9 wk. Retinal phosphatidylethanolamine was even more sensitive to the impact of the fish oil diet, with DHA levels in newborn rabbits rising from 10% (control diet) to 43% of total fatty acids. These results demonstrated that 22:5(n-6) in the normal rabbit retina remains elevated (compared with other species) at all ages even as retinal DHA increases. The great increase of DHA in newborns whose mothers were fed fish oil suggests placental transfer of DHA and incorporation into retinal lipids.     

Modulation of essential (n-6):(n-3) fatty acid ratios alters fatty acid status but not bone mass in piglets

Dietary (n-6) and (n-3) fatty acids have been implicated as important regulators of bone metabolism. The main objective of this research was to define the response of whole-body growth, fatty acid status and bone mass to a reduced dietary (n-6):(n-3) fatty acid ratio. A secondary objective was to determine whether there is an amount of fat x fatty acid ratio interaction for these outcomes. Piglets (n = 32) were randomized to 1 of 4 diets: group 1: [30 g fat/L + (n-6):(n-3) ratio 4.5:1]; group 2: [30 g fat/L + (n-6):(n-3) ratio 9.0:1]; group 3: [60 g fat/L + (n-6):(n-3) ratio 4.5:1]; and group 4: [60 g fat/L + (n-6):(n-3) ratio 9.0:1]. After 21 d, outcomes assessed included growth, fatty acid status and bone mass and metabolism. Growth and bone mass did not differ among the four groups nor did arachidonic acid (AA as g/100 g fatty acids) in plasma, adipose and brain. Piglets fed diets 1 and 3 with the lower (n-6):(n-3) ratio had lower liver AA (P < 0.001). Those fed diets 1 and 2 containing 30 g fat/L had lower docosahexaenoic acid (DHA as g/100 g fatty acids) in liver (P < 0.001), plasma (P = 0.019) and adipose tissue (P = 0.045). However, piglets fed diets 1 and 3 had higher (P < 0.001) brain DHA than those fed diets with a higher (n-6):(n-3) ratio. Higher plasma DHA was associated with less bone resorption (r = -0.44, P = 0.01). Therefore, elevation of dietary (n-3) fatty acids supports growth and fatty acid status while not compromising bone mass. The results may be of relevance to the nutritional management of preterm infants whose DHA status is often too low and bone resorption too high.     

Highly unsaturated (n-3) fatty acids, but not alpha-linolenic, conjugated linoleic or gamma-linolenic acids, reduce tumorigenesis in Apc(Min/+) mice

We showed previously that dietary eicosapentaenoic acid [EPA, 20:5(n-3)] is antitumorigenic in the APC:(Min/+) mouse, a genetic model of intestinal tumorigenesis. Only a few studies have evaluated the effects of dietary fatty acids, including EPA and docosahexaenoic acid [DHA, 22:6(n-3)], in this animal model and none have evaluated the previously touted antitumorigenicity of alpha-linolenic acid [ALA, 18:3(n-3)], conjugated linoleic acid [CLA, 77% 18:2(n-7)], or gamma-linolenic acid [GLA, 18:3(n-6)]. Stearidonic acid [SDA, 18:4(n-3)], the Delta6-desaturase product of ALA, which is readily metabolized to EPA, has not been evaluated previously for antitumorigenic efficacy. This study was undertaken to evaluate the antitumorigenicity of these dietary fatty acids (ALA, SDA, EPA, DHA, CLA and GLA) compared with oleic acid [OA, 18:1(n-9)] at a level of 3 g/100 g in the diets of APC:(Min/+) mice and to determine whether any alterations in tumorigenesis correspond to alterations in prostaglandin biosynthesis. Tumor multiplicity was significantly lower by approximately 50% in mice fed SDA or EPA compared with controls, whereas less pronounced effects were observed in mice fed DHA (P: = 0.15). ALA, CLA and GLA were ineffective at the dose tested. Although lower tumor numbers coincided with significantly lower prostaglandin levels in SDA- and EPA-fed mice, ALA and DHA supplementation resulted in equally low prostaglandin levels, despite proving less efficacious with regard to tumor number. Prostaglandin levels did not differ significantly in the CLA and GLA groups compared with controls. These results suggest that SDA and EPA attenuate tumorigenesis in this model and that this effect may be related in part to alterations in prostaglandin biosynthesis.     

Dietary n-3 polyunsaturated fatty acids: modification of rat cardiac lipids and fatty acid composition

The effects of 5, 10 and 20% dietary menhaden oil (MO) on the composition of heart lipid classes and fatty acids were studied. Male Sprague-Dawley rats were fed ad libitum 0, 5, 10 and 20% MO for 3 wk. The heart phosphoglyceride content and composition and cholesterol were unchanged by dietary MO. A nonlinear dose-response relationship was observed between dietary MO levels and fatty acid compositional changes. Cardiolipin, choline (PC), ethanolamine (PE) and serine/inositol (PS/PI) phosphoglycerides showed an incorporation of n-3 fatty acids, eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3), between the control and 5% MO group, a plateau between the 5 and 10% MO groups and a further increase at the 20% MO level. The initial reduction in 20:4n-6 content remained unchanged as dietary MO increased except in PE where a further reduction was found at the 20% MO level. Dietary MO did not significantly change the 20:4n-6 content in neutral lipids. Linoleic acid content was most resistant to dietary MO removal. The level of 18:2n-6 was significantly lowered in heart PC when rats were fed 10% MO. No significant differences were found in PS/PI. In PE and NL significant differences occurred only when rats were fed 20% MO. The significant fatty acid modifications of heart lipid and PL found between the control and lowest level of dietary MO (5%) suggest that dietary fish oil supplementation in human diets may not be required for this effect.     

Human milk: maternal dietary lipids and infant development

Human milk provides all the dietary essential fatty acids, linoleic acid (LA; 18:2n-6) and alpha-linolenic acid (18:3n-3), as well as their longer-chain more-unsaturated metabolites, including arachidonic acid (20:4n-6) and DHA (22:6n-3) to support the growth and development of the breast-fed infant. Human milk levels of LA have increased in Westernized nations from mean levels (g/100 g total fatty acids) of 6 to 12-16 over the last century, paralleling the increase in dietary intake of LA-rich vegetable oils. DHA levels (g/100 g total milk fatty acids) vary from 1% and are lowest in countries in which the intake of DHA from fish and other animal tissue lipids is low. The role of DHA in infant nutrition is of particular importance because DHA is accumulated specifically in the membrane lipids of the brain and retina, where it is important to visual and neural function. An important question is the extent to which many human diets that contain low amounts of n-3 fatty acids may compromise human development. The present paper reviews current knowledge on maternal diet and human milk fatty acids, the implications of maternal diet as the only source of essential fatty acids for infant development both before and after birth, and recent studies addressing the maternal intakes and milk DHA levels associated with risk of low infant neural system maturation.     

Comparison of the peripartum and postpartum phospholipid polyunsaturated fatty acid profiles of lactating and nonlactating women

BACKGROUND: Pregnancy is associated with increased absolute amounts of docosahexaenoic acid (DHA; 22:6n-3) in plasma phospholipids. Expressed as a proportion of total fatty acids, DHA declines slightly in late pregnancy but little information is available on the normalization of DHA postpartum, which may be different in lactating and nonlactating women. OBJECTIVE: The aim was to investigate maternal plasma and erythrocyte long-chain polyunsaturated fatty acids (long-chain polyenes; LCPs) postpartum, particularly DHA, in relation to lactation and dietary LCP intake. DESIGN: Healthy pregnant women who intended to breast-feed or exclusively bottle-feed their infants were studied at 36-37 wk of pregnancy. Blood samples were collected at entry, after parturition on days 2 and 5, and 1, 2, 4, 8, 16, 32, and 64 wk postpartum. Fatty acid profiles were analyzed in plasma and erythrocyte phospholipids. Dietary intakes were assessed 4 and 32 wk postpartum with a validated food-frequency questionnaire. RESULTS: After delivery, the percentages of plasma linoleic, arachidonic, eicosapentaenoic, and docosapentaenoic acids increased over time, whereas the percentage of docosapentaenoic acid decreased; the patterns of change did not differ significantly between the lactating and nonlactating groups. The percentage of DHA in plasma and erythrocyte phospholipid fatty acids declined significantly in the 2 groups, more so in the lactating women, and was enhanced when the lactation period was extended. Despite the apparent higher dietary intake of essential fatty acids in the lactating group at week 4, it was not significantly different from that of the nonlactating group. CONCLUSION: Normalization of maternal plasma and erythrocyte phospholipid n-3 LCPs differs significantly between lactating and nonlactating women postpartum but that of n-6 LCPs does not.     

Metabolism of stearidonic acid in human subjects: comparison with the metabolism of other n-3 fatty acids

BACKGROUND: For many persons who wish to obtain the health benefits provided by dietary n-3 fatty acids, daily ingestion of fish or fish oil is not a sustainable long-term approach. To increase the number of sustainable dietary options, a land-based source of n-3 fatty acids that is effective in increasing tissue concentrations of the long-chain n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is required. OBJECTIVE: The objective of the study was to examine the ability of dietary stearidonic acid (SDA) to increase tissue concentrations of EPA and DHA in healthy human subjects and to compare the effectiveness of SDA with that of the n-3 fatty acids alpha-linolenic acid (ALA) and EPA. DESIGN: Encapsulated SDA, ALA, or EPA was ingested daily in doses of 0.75 g and then 1.5 g for periods of 3 wk each by healthy male and postmenopausal female subjects (n = 15/group) in a double-blind, parallel-group design. RESULTS: Dietary SDA increased EPA and docosapentaenoic acid concentrations but not DHA concentrations in erythrocyte and in plasma phospholipids. The relative effectiveness of the tested dietary fatty acids in increasing tissue EPA was 1:0.3:0.07 for EPA:SDA:ALA. CONCLUSIONS: Vegetable oils containing SDA could be a dietary source of n-3 fatty acids that would be more effective in increasing tissue EPA concentrations than are current ALA-containing vegetable oils. The use of SDA-containing oils in food manufacture could provide a wide range of dietary alternatives for increasing tissue EPA concentrations.     

Maternal plasma phospholipid polyunsaturated fatty acids in pregnancy with and without gestational diabetes mellitus: relations with maternal factors.

BACKGROUND: The fatty acids arachidonic acid (AA; 20:4n-6) and docosahexaenoic acid (DHA; 22:6n-3) are essential for fetal growth and development, but their metabolism may be altered in insulin resistance. OBJECTIVES: The objectives were to determine maternal plasma phospholipid polyunsaturated fatty acid concentrations in pregnant women receiving dietary therapy for gestational diabetes mellitus (GDM) and to identify maternal factors associated with plasma phospholipid AA and DHA concentrations in the third trimester. DESIGN: Fasting plasma phospholipid fatty acids were determined in women with GDM (n = 15) receiving dietary therapy only and in healthy, pregnant women without GDM (control group, n = 15) at 27-30, 33-35, and 36-39 wk gestation. RESULTS: Maternal plasma phospholipid (as % by wt of total fatty acids and mg/L) linoleic acid (18:2n-6), AA, and 22:5n-6 concentrations did not differ significantly between women with GDM and control subjects. The other n-6 long-chain polyunsaturated fatty acids (% by wt) were lower in GDM subjects than in control subjects. Plasma phospholipid (expressed as % by wt and mg/L) linolenic acid (18:3n-3) and summed precursors of DHA were lower and DHA (% by wt and mg/L), adjusted for dietary DHA intake, was 13% higher in GDM subjects than in control subjects. Maternal blood hemoglobin A1C was inversely related to plasma phospholipid AA (% by wt) (r = -0.56, P = 0.03) in control subjects and positively associated with plasma phospholipid AA (% by wt) in women with GDM (r = 0.76, P = 0.001). Pregravid body mass index was negatively associated with plasma phospholipid DHA (% by wt) in control subjects (r = -0.55, P = 0.04) and in women with GDM with a body mass index (in kg/m2) <30 (r = -0.76, P = 0.007). CONCLUSIONS: This is the first report documenting alterations in maternal plasma phospholipid PUFAs in pregnant women receiving dietary therapy for GDM. In pregnant woman, both with and without GDM, maternal glycemic control and pregravid BMI appear to be significant predictors of plasma phospholipid AA and DHA, respectively, during the third trimester. Additionally, dietary DHA significantly affects phospholipid DHA concentrations.     

Role of n-3 fatty acids in prevention of disease complications in patients with HIV.

Hypertriglyceridemia and insulin resistance have been seen in patients with HIV. Beneficial effects of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported for these conditions. One study of n-3 fatty acid supplementation in patients with HIV reported a decrease in serum triglyceride levels. These marine fatty acids appear to be working at a number of sites to achieve an improvement in lipid metabolism and insulin sensitivity. There is disagreement about the amount of n-3 fatty acids needed to achieve different effects and about the optimal ratio of dietary n-6 and n-3 fatty acids.     

不同膳食脂肪酸对大鼠乳腺癌组织脂肪酸组成和脂代谢基因表达的影响

目的探讨不同膳食脂肪酸组成影响大鼠乳腺癌发生、发展的可能分子机制。方法用8种不同膳食脂肪酸组成(SFA、MUFA、n-6PUFA、n-3PUFA、1∶1n-6/n-3、5∶1n-6/n-3、10∶1n-6/n-3、1∶2∶1S/M/P其中n-6/n-31∶1)喂养SD雌性大鼠,并在大鼠乳腺癌模型的基础上,用气相色谱内标法观察大鼠乳腺组织脂肪酸组成改变,RT-PCR分析组织脂代谢调控基因(FAS、COX-2和5-LOX)的表达。结果在不同膳食脂肪酸构成中,只有1∶1n-6/n-3能有效抑制大鼠乳腺癌的发生。不同膳食脂肪酸构成可导致大鼠乳腺组织脂肪酸组成发生相应变化,且各组间的脂肪酸含量有显著差异。高乳腺癌诱发的SFA、MUFA、n-6PUFA、5∶1n-6/n-3、10∶1n-6/n-3和1∶2∶1S/M/P喂养组乳腺组织含有较多的C18∶1、C18∶2和C20∶4,而EPA和DHA含量极少。无或低乳腺癌诱发的n-3PUFA和1∶1n-6/n-3喂养组乳腺组织EPA和DHA明显增多,C20∶4含量显著减少。RT-PCR结果显示1∶1n-6/n-3低诱癌组较相应对喂组上调FAS、COX-2和5-LOXmRNA表达力度明显弱于其它高乳腺癌诱发组。结论不同膳食脂肪酸组成能明显改变大鼠乳腺组织脂肪酸组成,进而影响脂代谢基因FAS、COX-2和5-LOX表达,可能是大鼠乳腺癌发生的分子机制之一。     

Total fat intake modifies plasma fatty acid composition in humans

Plasma fatty acid composition reflects dietary fatty acids. Whether the total fat content of the diet alters the fatty acid composition of plasma phospholipid, cholesteryl ester, triacylglycerol and free fatty acids is unknown. To evaluate the effects of low versus high fat diets on plasma fatty acids, a 12-wk, randomized, crossover, controlled feeding trial was conducted in healthy men and women with isoenergic low fat (20% energy) and high fat (45% energy) diets containing constant proportions of fatty acids. Ten subjects consumed one experimental diet for 28 d, their usual diet for 4 wk and the alternate experimental diet for 28 d. Endpoint measures of plasma fatty acids were determined at the end of each experimental period. The effects of the two diets were compared within subjects by analysis of variance. Plasma fatty acids (%) varied in response to total dietary fat with significantly greater total polyunsaturated fat, (n-6) and 18:2(n-6) levels in phospholipids and cholesteryl esters after high fat dietary consumption. The low fat diet was associated with significantly greater total (n-3) fatty acids, 20:5(n-3) and 22:6(n-3) levels in plasma phospholipid fatty acids and cholesteryl esters. Consumption of a low fat diet alters fatty acid patterns in a manner similar to that observed with feeding of (n-3) long-chain fatty acids. This change is likely related to decreased competition for the enzymes of elongation and desaturation, with reduced total intake of 18:2(n-6) favoring elongation and desaturation of available (n-3) fatty acids.     

Effect of altered dietary n-6-to-n-3 fatty acid ratio on erythrocyte lipid composition and membrane-bound enzymes

Three experimental diets with varied n-6-to-n-3 fatty acid ratios (120, 40 and 8) were prepared by a suitable blending of safflower oil containing 72.5% linoleic (18:2 n-6) acid and non-detectable levels of alpha-linolenic (18:3 n-3) acid, and soybean oil having 56.1% linoleic (18:2 n-6) acid and 7.9% alpha-linolenic (18:3 n-3) acid. These diets were fed to weanling female Wistar/NIN (inbred) rats for 16 wk to assess the impact of altered dietary n-6-to-n-3 fatty acid ratio on erythrocyte membrane (EMS) cholesterol, phospholipids, fatty acid composition and activities of membrane-bound enzymes such as Na+,K+-ATPase, Ca2+, Mg2+-ATPase and acetylcholinesterase. Activities of total and ouabain-sensitive-ATPases were significantly higher in the erythrocyte membranes of rats fed diets with a n-6-to-n-3 fatty acid ratio of 40 compared to other groups, whereas the erythrocyte membrane-bound acetylcholinesterase was significantly different among the three groups. The highest and lowest activities for this enzyme were observed in the dietary groups with n-6-to-n-3 fatty acid ratios of 8 and 40 respectively. However, the EMS of rats fed diets with a n-6-to-n-3 fatty acid ratio of 40 alone had significantly higher Ca2+,Mg2+-ATPase compared to those of other two groups. Significant increases were observed in absolute amounts of cholesterol, phospholipids and molar ratio of cholesterol to phospholipids in the EMS of rats fed a diet with a very high 18:2 n-6-to-18:3 n-3 fatty acid ratio (120) as compared to those from the dietary group with 18:2 n-6-to-18:3 n-3 fatty acid ratio (40), which had the lowest levels of cholesterol, phospholipids and cholesterol-to-phospholipid molar ratio. On the other hand, the EMS from rats fed a diet with a very low n-6-to-n-3 fatty acid ratio (8) had significantly lower cholesterol and higher proportions of stearic (18:0), oleic (18:1 n-9), eicosapentaenoic (20:5 n-3), and docosahexaenoic acids, and a higher ratio of docosahexaenoic (22:6 n-3) acid-to-a-linoleic (18:3 n-3) acid compared to the EMS from a very high n-6-to-n-3 fatty acid ratio of 120. Although these changes in EM fatty acid profiles were expected of the respective dietary regimens, the observed changes in the activities of membrane-bound enzymes could have resulted from their interaction with membrane cholesterol, phospholipids and fatty acyl chains.     

Depression and long chain n-3 fatty acids in adipose tissue in adults from Crete

BACKGROUND: Only one study has investigated the relationship of essential fatty acids in the adipose tissue with depression in adults and suggested an inverse relationship between docosahexaenoic acid (22:6 n-3) (DHA) and depression. OBJECTIVE: To examine the relation between adipose tissue polyunsaturated fatty acids especially n-3 and n-6 fatty acids, an index of long-term or habitual fatty acid intake, and depression in adults. DESIGN: Cross-sectional study of healthy adults from the island of Crete. SETTING: The Preventive Medicine and Nutrition Clinic, University of Crete, Greece. SUBJECTS: A total of 130 healthy adults (59 males, 71 females) aged 22-58 years. The sample was a sub-sample of the Greek ApoEurope study group. METHODS: Fatty acids were determined by gas chromatography in adipose tissue. Information about depression was obtained through the Zung Self-rating Depression Scale. RESULTS: Adipose tissue DHA was inversely related with depression. Multiple linear regression analysis taking into account the possible confounding effect of age, gender, body mass index, smoking and educational level confirmed this association. CONCLUSIONS: The inverse relationship between adipose DHA and depression in adults, replicates findings of a previous study. This relationship indicates that a low long-term dietary intake of DHA is associated with an increased risk for depression in adults.     

Effects of olive oil and its fractions on oxidative stress and the liver's fatty acid composition in 2,4-Dichlorophenoxyacetic acid-treated rats

Background

Dietary long-chain polyunsaturated fatty acids (LC-PUFA) are of crucial importance for the development of neural tissues. The aim of this study was to evaluate the impact of a dietary supplementation in n-3 fatty acids in female rats during gestation and lactation on fatty acid pattern in brain glial cells phosphatidylethanolamine (PE) and phosphatidylserine (PS) in the neonates.

Methods

Sprague-Dawley rats were fed during the whole gestation and lactation period with a diet containing either docosahexaenoic acid (DHA, 0.55%) and eicosapentaenoic acid (EPA, 0.75% of total fatty acids) or α-linolenic acid (ALA, 2.90%). At two weeks of age, gastric content and brain glial cell PE and PS of rat neonates were analyzed for their fatty acid and dimethylacetal (DMA) profile. Data were analyzed by bivariate and multivariate statistics.

Results

In the neonates from the group fed with n-3 LC-PUFA, the DHA level in gastric content (+65%, P < 0.0001) and brain glial cell PE (+18%, P = 0.0001) and PS (+15%, P = 0.0009) were significantly increased compared to the ALA group. The filtered correlation analysis (P < 0.05) underlined that levels of dihomo-γ-linolenic acid (DGLA), DHA and n-3 docosapentaenoic acid (DPA) were negatively correlated with arachidonic acid (ARA) and n-6 DPA in PE of brain glial cells. No significant correlation between n-3 and n-6 LC-PUFA were found in the PS dataset. DMA level in PE was negatively correlated with n-6 DPA. DMA were found to occur in brain glial cell PS fraction; in this class DMA level was correlated negatively with DHA and positively with ARA.

Conclusion

The present study confirms that early supplementation of maternal diet with n-3 fatty acids supplied as LC-PUFA is more efficient in increasing n-3 in brain glial cell PE and PS in the neonate than ALA. Negative correlation between n-6 DPA, a conventional marker of DHA deficiency, and DMA in PE suggests n-6 DPA that potentially be considered as a marker of tissue ethanolamine plasmalogen status. The combination of multivariate and bivariate statistics allowed to underline that the accretion pattern of n-3 LC-PUFA in PE and PS differ.