二十碳五烯酸改变JurkatT细胞膜脂肪微区域脂肪环境的研究

目的:研究二十碳五烯酸(EPA)处理后T细胞膜脂肪微区域中脂肪酸组成改变及其对磷脂分子中脂肪酰基取代基团的作用。方法:用不连续蔗糖密度梯度超速离心法分离T细胞膜脂肪微区域,然后用气相色谱分析细胞膜亚区域中脂肪酸组成,高效液相质谱联用测定膜脂肪微区域磷脂分子脂肪酸酰基取代基团的构成。结果:EPA处理使T细胞脂肪微区域中多不饱和脂肪酸(PUFAs),n-3PUFAs和n-3PUFAs/n-6PUFAs的比值升高;磷脂分子中除了鞘磷脂以外,其他的磷脂分子如磷脂酰胆碱、磷脂酰乙醇胺、磷脂酰丝氨酸、磷脂酰肌醇分子中一些脂肪酰取代基团有显著改变。结论:EPA处理明显改变T细胞膜脂肪微区域和可溶膜组分中脂肪酸的组成,改变磷脂分子脂肪酰基取代基团的构成,从而改变细胞膜脂肪微区域的脂肪环境。     

Comparative evaluation of essential fatty acid composition of mothers' milk of some urban and suburban regions of West Bengal,India

This study investigated the fatty acid composition of lipid present in breast milk of mothers residing in urban and suburban regions of West Bengal with special emphasis on n-6 and n-3 polyunsaturated fatty acids, which played a crucial role in the growth and development of neonates. Milk samples collected from 135 mothers of middle income group (average monthly income around ‘Rs 10,000/-’) were analysed by gas liquid chromatography after extraction and transmethylation to determine fatty acid composition. Information about the dietary intake of individual mothers was obtained through food frequency questionnaire. The fractions of n-6 and n-3 polyunsaturated fatty acids available in milk of urban mothers were 13.59 ± 0.94 and 3.65 ± 0.49, respectively, and in suburban mothers 12.74 ± 0.89 and 4.36 ± 0.39, respectively. The green leafy vegetables, fishes and vegetable oils were the major sources of essential fatty acids in the diet of the experimental groups of Bengali mothers. This study revealed a relationship between the alimentary habits of mothers and the concentration of essential fatty acids in breast milk of Bengali mothers.     

Perinatal Polyunsaturated Fatty Acid Status and Obesity Risk

High obesity rates in almost all regions of the world prompt an urgent need for effective obesity prevention. Very good scientific evidence from cell culture and rodent studies show that the availability of essential polyunsaturated fatty acids (PUFA) and their long-chain polyunsaturated derivatives, namely, arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid, influence adipogenesis; for this reason, early life status may influence later obesity risk. The respective PUFA effects could be mediated via their eicosanoid derivatives, their influence on cell membrane properties, the browning of white adipose tissue, changes to the offspring gut microbiome, their influence on developing regulatory circuits, and gene expression during critical periods. Randomized clinical trials and observational studies show divergent findings in humans, with mostly null findings but also the positive and negative effects of an increased n-3 to n-6 PUFA ratio on BMI and fat mass development. Hence, animal study findings cannot be directly extrapolated to humans. Even though the mechanistic data basis for the effects of n-3 PUFA on obesity risk appears promising, no recommendations for humans can be derived at present.     

Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in peripheral arterial disease

BACKGROUND AND AIMS: epidemiological studies suggest polyunsaturated fatty acids protect against the development of atherosclerosis. The aim of this study was to perform a randomized controlled trial of gamma-linolenic and eicosapentaenoic acids in patients with lower limb atherosclerosis. Main outcome measures were: cholesterol and lipoprotein concentrations; haemostatic and rheological variables; the ankle brachial pressure index; walking distance; and cardiovascular events and death. METHODS: 120 men and women with stable intermittent claudication were randomized to 2 years treatment with either a combination of gamma-linolenic and eicosapentaenoic acids, or placebo. RESULTS: 39 (65.0 cent) of those taking fatty acids and 36 (60.0 cent) of those taking placebo completed the trial. Lipid concentrations did not differ significantly during the trial. In those taking fatty acids, haematocrit was significantly higher than in the placebo group after 6 months (46.1 cent compared with 44.6 cent, P 0.05). CONCLUSIONS: a combination of polyunsaturated fatty acids produced a statistically significant reduction in systolic blood pressure, but no other significant benefits on risk factors. The trend towards fewer coronary events in those taking fatty acids warrants further investigation.     

不同年龄阶段小鼠脑聚集二十二碳六烯酸及脂肪酸去饱和酶的变化

【目的】 探讨生命早期不同年龄阶段脑摄取、聚集二十二碳六烯酸(DHA)(C22:6n-3)及相关去饱和酶的变化。 【方法】 使用6~8周龄清洁级C57BL/6J雌性小鼠,分别给予n-3 多不饱和脂肪酸(n-3 PUFAs)缺乏饲料和含n-3 PUFAs饲料喂养6周,然后雌雄合笼交配繁殖,新生仔鼠分别于生后7、21 d和42 d时取血、脑和肝脏。采用甲酯化-气相色谱分析对血浆、脑和肝脏中脂肪酸谱进行分析;采用荧光定量PCR方法对脑和肝脏中脂肪酸去饱和酶1(FADS1)和脂肪酸去饱和酶2(FADS2)基因mRNA表达进行检测。 【结果】 对不同年龄小鼠组织脂肪酸的比较发现,脑中DHA和总n-3 PUFAs含量在两种不同饲料组均随年龄增加而升高;而肝中的含量则随年龄增加而降低。与n-3 PUFAs缺乏组相比,饲料中添加n-3 PUFAs可使仔鼠生后7、21 d和42 d时脑和肝脏中DHA和总n-3 PUFAs含量均显著升高;升高的程度在脑组织中随年龄增加而降低,而在肝脏组织中则不随年龄变化。对不同年龄段FADS表达的比较发现,FADS1和FADS2 mRNA在脑组织中的表达量于42 d时显著高于7 d和21 d,而在肝组织中的表达量于各年龄段之间无显著性差异。与n-3 PUFAs缺乏组相比,饲料中添加n-3 PUFAs可使仔鼠生后7 d和21 d时脑组织FADS1和FADS2表达水平显著降低,而42 d时的表达无变化;肝组织中这两种酶mRNA水平在7 d和21 d时无变化,42 d时FADS1显著降低。 【结论】 发育期脑对DHA的聚集需求随着年龄增大而逐渐减少;FADS在脑中的表达水平随年龄增大而升高。同时,饲料n-3 PUFAs缺乏状态对脑聚集DHA以及FADS的影响在年龄小时更明显。     

Omega-3 Polyunsaturated Fatty Acids Trigger Cell Cycle Arrest and Induce Apoptosis in Human Neuroblastoma LA-N-1 Cells

Omega-3 (n-3) fatty acids are dietary long-chain fatty acids with an array of health benefits. Previous research has demonstrated the growth-inhibitory effect of n-3 fatty acids on different cancer cell lines in vitro, yet their anti-tumor effects and underlying action mechanisms on human neuroblastoma LA-N-1 cells have not yet been reported. In this study, we showed that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) exhibited time- and concentration-dependent anti-proliferative effect on the human neuroblastoma LA-N-1 cells, but had minimal cytotoxicity on the normal or non-tumorigenic cells, as measured by MTT reduction assay. Mechanistic studies indicated that DHA and EPA triggered G₀/G₁ cell cycle arrest in LA-N-1 cells, as detected by flow cytometry, which was accompanied by a decrease in the expression of CDK2 and cyclin E proteins. Moreover, DHA and EPA could also induce apoptosis in LA-N-1 cells as revealed by an increase in DNA fragmentation, phosphatidylserine externalization and mitochondrial membrane depolarization. Up-regulation of Bax, activated caspase-3 and caspase-9 proteins, and down-regulation of Bcl-X_L protein, might account for the occurrence of apoptotic events. Collectively, our results suggest that the growth-inhibitory effect of DHA and EPA on LA-N-1 cells might be mediated, at least in part, via triggering of cell cycle arrest and apoptosis. Therefore, DHA and EPA are potential anti-cancer agents which might be used for the adjuvant therapy or combination therapy with the conventional anti-cancer drugs for the treatment of some forms of human neuroblastoma with minimal toxicity.     

Lipase inhibitor orlistat decreases incorporation of eicosapentaenoic and docosahexaenoic acids in rat tissues

Orlistat is a gastric and pancreatic lipases inhibitor that is often prescribed to obese subjects. Orlistat has been shown to decrease the absorption of biologically important lipophilic micronutrients such as liposoluble vitamins. We hypothesized that long-term administration of orlistat may lower the incorporation of n-3 long-chain polyunsaturated fatty acids (LC-PUFA) in blood lipids and tissues. This hypothesis was tested in rats fed a diet supplemented with fish oil as a source of n-3 LC-PUFA. Male Wistar rats (n = 18) were divided into 3 groups and fed experimental high-fat diets containing fish oil (control diet) or fish oil plus orlistat (200 and 400 mg/kg of diet) over the course of 3 weeks. Fat absorption and the level of eicosapentaenoic acid (EPA) and docosahexaenoic acid, among other fatty acids, in red blood cells, plasma, liver, and spleen, were measured at the end of the experimental period. The results show that at 200 mg and 400 mg/kg of diet orlistat lowers fat absorption by 9% (P = .008) and 54% (P = .008). Orlistat given at the higher level induced a reduction of the incorporation of EPA in red blood cell (−45%; P = .006) and in plasma (−34%; P = .026) compared to the control group. Our results confirmed that administration of orlistat reduces incorporation of n-3 LC-PUFA in blood lipids and tissues in a rat model.     

Eicosapentaenoic acid ethyl ester supplementation in cachectic cancer patients and healthy subjects: effects on lipolysis and lipid oxidation

BACKGROUND & AIMS: Recent reports suggest that weight loss in cachectic cancer patients may be inhibited by supplementation of the n-3 fatty acid eicosapentaenoic acid (20:5n-3; EPA), presumably due to inhibition of lipolysis. The aim of the present double-blind, randomized trial was to assess whether short-term oral EPA ethyl ester (EE) supplementation inhibits lipolysis and lipid oxidation in weight-losing cancer patients and in healthy subjects. METHODS: Seventeen weight-losing, cancer patients of different tumor types, and 16 healthy subjects were randomized to receive EPA-EE (6 g/d) or placebo (oleic acid (OA)-EE; 6 g/d) for seven days. At baseline (day 0) and during supplementation (days 2 and 7) whole-body lipolysis and palmitic acid release were measured in the overnight fasting state using [1, 1, 2, 3, 3-(2)H(5)]glycerol and [1-(13)C]palmitic acid. Palmitate oxidation was determined by measuring(13)CO(2)enrichment in expired breath. RESULTS: No significant effects of EPA-EE on whole-body lipolysis, palmitic acid release, or palmitate oxidation were detected in cancer patients nor in healthy subjects in comparison with OA-EE. EPA-EE supplementation reduced plasma-free fatty acid and triacylglycerol concentrations significantly in healthy subjects but not in cancer patients. CONCLUSION: We conclude that supplementation of EPA-EE does not significantly inhibit lipolysis or lipid oxidation in weight-losing cancer patients or in healthy subjects during short-term supplementation when using OA-EE as a placebo supplement.     

Benefits of Structured and Free Monoacylglycerols to Deliver Eicosapentaenoic (EPA) in a Model of Lipid Malabsorption

In the present study, we used a preclinical model of induced lipolytic enzyme insufficiency, and hypothesized that the use of monoacylglycerols (MAG) will enhance their bioavailability and delivery to the tissues. Experimental diets containing 20% lipids were fed to rats for 21 days with or without Orlistat. The control diet of fish oil (FO), a source of EPA and DHA, was tested against: structured (A) vanillin acetal of sn-2 MAG (Vanil + O) and (B) diacetyl derivative of sn-2 MAG (Acetyl + O) and (C) free MAG (MAG + O). FA profiles with an emphasis on EPA and DHA levels were determined in plasma, red blood cells (RBC), liver, spleen, brain and retina. We observed significant reduction of lipid absorption when rats co-consumed Orlistat. As expected, the FO groups with and without Orlistat showed the biggest difference. The Vanil + O, Acetyl + O and MAG + O groups, demonstrated higher levels of EPA (5.5 ± 1.9, 4.6 ± 1.6 and 5.6 ± 0.6, respectively) in RBC compared with FO + O diets (3.3 ± 0.2, 2.6 ± 0.2). Levels of EPA incorporation, in plasma, were similar to those obtained for RBC, and similar trends were observed for the collected tissues and even with DHA levels. These observations with two MAG derivatives providing the fatty acid esterified in the sn-2 position, show that these molecules are efficient vehicles of EPA in malabsorption conditions which is in line with our hypothesis. Free MAG, characterized as having exclusively sn-1(3) isomers of EPA, demonstrated better absorption efficiencies and accretion to tissues when compared to structured MAG. The study demonstrated that structured and free MAG can be used efficiently as an enteral vehicle to supply bioactive fatty acids such as EPA and DHA in lipid malabsorption where diminished lipolytic activity is the underlying cause.     

中国三地区人成熟母乳脂肪酸含量的研究

目的分析中国处于三个不同地理环境地区的母体成熟乳中脂肪酸含量的差异。方法选取江苏句容(河湖地区)、山东日照(沿海地区)和河北徐水(内陆地区)三地,每地区募集40～50名健康产妇,于产后第28天采集母乳,Folch法提取其中脂肪,气相色谱法分析其中31种脂肪酸构成及含量。结果句容,日照和徐水分别募集到47、50和46名受试者,各地成熟乳中饱和脂肪酸(SFA)、单不饱和脂肪酸(MUFA)、n-6多不饱和脂肪酸(n-6PUFA)和n-3多不饱和脂肪酸(n-3PUFA)的主要成份均分别为C16∶0、C18∶1 n-9cis、C18∶2 n-6 cis和C18∶3 n-3。三地区成熟乳中花生四烯酸(ARA)百分含量中位数分别为0.72%、0.63%和0.63%;二十二碳六烯酸(DHA)分别为0.41%、0.47%和0.24%。三地区总乳脂含量中位数分别为4.47、1.50和3.91g/100g母乳;其总脂肪酸含量中位数分别为3934、1319和3437mg/100g母乳,日照总乳脂含量和总脂肪酸含量显著低于另两地区。结论母体成熟乳中脂肪酸含量及构成存在显著地区差异性。     

二十碳五烯酸影响T细胞膜脂肪微区域中IL-2受体的分布

目的:研究二十碳五烯酸(EPA)对T细胞膜脂肪微区域(lipidrafts)中IL-2受体(IL-2R)分布的影响。方法:EPA(20︰5)处理JurkatE6-1T细胞为实验组,硬脂酸(18:0)处理为阴性对照。用流式细胞仪检测对T细胞表面分子CD25(IL-2α受体)表达的抑制作用。应用蛋白免疫印迹分析,化学发光法检测IL-2α受体所在的T细胞膜脂肪微区域分离组分。结果:用硬脂酸处理T细胞,细胞表面CD25阳性表达细胞为39.53%,不同浓度的EPA(5、12.5、25,50、75μmol/L)处理,CD25阳性表达细胞分别为36.12%、31.30%、23.59%、16.67%和11.65%,EPA可抑制T细胞表面分子CD25的表达。蛋白印迹分析确定IL-2α、IL-2Rβ和IL-2Rγc都存在于微区域组分中,EPA处理使部分IL-2Rα、IL-2Rβ和IL-2Rγc从膜脂肪微区域移位到可溶膜区域。结论:膜脂肪微区域为IL-2受体信号传导的功能性亚区域,EPA通过调节IL-2Rα、IL-2Rβ和IL-2Rγc在膜脂肪微区域的分布,使部分IL-2R从功能性脂肪微区域移位到非功能性可溶膜区域,而产生免疫抑制作用。     

Role for fatty acid binding protein in the regulation of hepatic lipogenesis by dietary linoleic acid

The effect of added dietary ethyl palmitate or ethyl linoleate on hepatic lipogenic enzymes and the amount of hepatic fatty acid binding protein was examined in meal-fed rats. Dietary linoleate reduced the activities of fatty acid synthetase, glucose-6-phosphate dehydrogenase, NADP-malic enzyme, ATP-citrate lyase, and the amount of fatty acid binding protein compared to rats fed a fat-free or palmitate supplemented diet. The possible role of fatty acid biding protein in the regulation of lipogenesis by dietary fat is discussed.     

Fatty acid composition in preterm and term breast milk

The aim of this study was to determine and compare the fatty acid (FA) composition of colostrum and mature milk produced by nursing mothers of preterm and at-term newborns, in Florianópolis, SC, Brazil. Low contents of Eicosapentaenoic acid (EPA) (0.02%/colostrum and 0.01%/mature milk for preterm and term milk) and Docosahexaenoic acid (DHA) (colostrum group: 0.10%/preterm and 0.09%/term; mature milk: 0.05%/preterm and 0.03%/term) were determined. The comparison among the groups showed that the elaidic acid content was significantly higher (1.67%) in mature term milk. The content of rumenic acid (conjugated linoleic acid) was significantly higher in at-term colostrum compared with preterm colostrum. When considering the maturity of the milk, there was a significant increase in the percentage of this FA in the preterm group. The results show that, overall, the greatest differences observed were between the colostrums and mature milks for both groups and not between preterm and at-term mothers.     

口服补充n-3多不饱和脂肪酸对糖尿病病人血糖和血脂影响的Meta分析

目的:系统评价糖尿病病人添加富含n-3多不饱和脂肪酸(PUFA)的营养补充剂是否可以改善病人血糖和血脂的状况. 方法:检索MEDMNE、EMBASE、Cochrane对照试验中心注册数据库(CENTRAL),检索语言为英语,检索起止时间为2000年至2014年.检索词为Diabetes,n-3 polyunsaturated fatty acid,fish oil,clinical trial.纳入对糖尿病病人添加n-3 PUFA的随机对照试验,采用Jadad量表进行研究质量评价,使用RevMan 5.2软件进行Meta分析. 结果:最终纳入6项来自5个国家的高质量研究数据资料.n-3 PUFA组病人血清瘦素水平低于对照组,且差异有统计学意义.随机血糖、糖化血红蛋白、胰岛素、三酰甘油、胆固醇、高密度脂蛋白、低密度脂蛋白和脂联素等,两组之间差异均无统计学意义. 结论:现有临床证据不能证明膳食补充n-3 PUFA对改善糖尿病病人的血糖和血脂状况有益.     

Horse meat consumption affects iron status,lipid profile and fatty acid composition of red blood cells in healthy volunteers

This study investigated the effect of moderate consumption of horse meat on iron status, lipid profile and fatty acid composition of red blood cells in healthy male volunteers. Fifty-two subjects were randomly assigned to two groups of 26 subjects each: a test group consuming two portions of 175 g/week of horse meat, and a control group that abstained from eating horse meat during the 90 days trial. Before and after 90 days, blood samples were collected for analysis. Horse meat consumption significantly (p ≤ 0.05) reduced serum levels of total and low-density lipoprotein cholesterol ( ? 6.2% and ? 9.1%, respectively) and transferrin ( ? 4.6%). Total n ? 3, long chain polyunsaturated fatty acids n ? 3 and docosahexeanoic acid content in erythrocytes increased (p ≤ 0.05) by about 7.8%, 8% and 11%, respectively. In conclusion, the regular consumption of horse meat may contribute to the dietary intake of n ? 3 polyunsaturated fatty acids and may improve lipid profile and iron status in healthy subjects.     

Seasonal variability in intake of fish oil dietary supplements among inhabitants of Warsaw

The aim of this study was to estimate the rate of sale and intake level of dietary supplements containing fish oil among inhabitants of Warsaw. The survey was carried out during 25 months in the years 2004 to 2006 in 3 selected drugstores localized in the central areas of Warsaw. The amount of fish oil, level of ω-3 long-chain polyunsaturated fatty acids declared on the label, price and rate of sale of particular supplements, as well as the reasons why customers purchased the supplements were collected and analyzed. The rate of sale of fish oil supplements was low; however, it showed a tendency for increase during the time of evaluation. Strong seasonal variability of supplements sale and therefore intake were observed. The highest levels for these parameters occurred from October to February and the lowest from May to July. The most often purchased supplements were fish liver oil capsules. The main reason for fish oil supplement purchases was medical recommendations. The health benefits of fish liver oil were known among customers of drugstores; however, the term ω-3 was almost unknown.     

Bioavailability of long-chain omega-3 polyunsaturated fatty acid enriched luncheon meats

(Nutr Diet 2005;62:130–137) Objective: To determine the acute and chronic effects of low doses of long chain (LC) n‐3 polyunsaturated fatty acids (PUFA) on plasma LC n‐3 PUFA levels. Design: In the acute study, six healthy omnivores, avoiding fish meals on the day prior to the study, provided a fasting blood sample initially and post prandially at four hours. In the chronic study, 12 healthy subjects provided a fasting blood sample at baseline and three weeks after daily consumption of the test food. Main outcome measures: Plasma non‐esterified fatty acid and phospholipid LC n‐3 PUFA composition. Statistical analysis: Differences in plasma non‐esterified fatty acids and phospholipid LC n‐3 PUFA. A pre‐ and post‐consumption of the test food were assessed using paired t‐tests (spss ). Results: The acute study demonstrated that a low dose of LC n‐3 PUFA (25% eicosapentaenoic acid and 75% docosahexaenoic acid) significantly increased eicosapentaenoic acid levels in plasma of human subjects postprandially from 0.30% to 0.42% of total non‐esterified fatty acids, a per cent change of 39% (P < 0.05). The chronic study demonstrated a significant increase in total n‐3 phospholipids from zero weeks (5.48% of total fatty acids) to three weeks (7.92% of total fatty acids), representing a per cent increase of 44% (P = 0.006). The n‐6 to n‐3 ratio of LC PUFA phospholipids demonstrated a significant reduction from 5.1 at zero weeks to 4.07 at three weeks, representing a reduction of 20% (P = 0.006). Conclusions: These findings demonstrate the bioavailability of LC n‐3 PUFA consumed as a low‐fat omega‐3‐enriched luncheon meat.