膳食脂肪酸构成对小鼠淋巴细胞功能和脂质过氧化的影响

目的:探讨膳食多不饱和脂肪酸n-6/n-3比值对小鼠T淋巴细胞功能和脂质过氧化的影响。方法:96只BALb/c小鼠随机分为8组:饱和脂肪酸:单不饱和脂肪酸:多不饱和脂肪酸(S∶M∶P)为1:1.5:3.7和1:1.5:1,n-6/n-3比值分别为1、7.5、15、30,各4组。基础饲料采用AIN-93G配方,各组饲料的脂肪酸构成以食用油脂调配。饲养12w。测定小鼠T淋巴细胞功能,IL-2和血清丙二醛(MDA)水平。结果:S:M:P为1:1.5∶3.7,n-6/n-3为1时,小鼠T淋巴细胞增殖活性、IL-2水平均显著降低(P<0.05),且两者显著正相关(r=0.438,P<0.05),n-6/n-3为1、30时,血清MDA水平明显高于n-6/n-3为7.5和15组(P<0.05);S:M:P为1:1.5:1,n-6/n-3为1时,小鼠T淋巴细胞增殖活性、CD4+/CD8+T细胞比例、IL-2水平明显降低(P<0.05),n-6/n-3为1、30时,血清MDA水平明显高于n-6/n-3为7.5组(P<0.05)。结论:S:M:P为1:1.5:3.7和1:1.5:1,n-6/n-3为1时,T淋巴细胞功能受到抑制,其作用机制可能与IL-2有关;DHA对CD4+/CD8+T细胞比例的抑制作用可能大于ALA;结合脂质过氧化程度来考虑,膳食n-6/n-3为7.5～15范围内较为理想。     

脂肪酸水平与儿童注意缺陷多动障碍的关系及膳食补充n-3类脂肪酸的影响

目的研究儿童注意缺陷多动障碍(ADHD)与非ADHD儿童体内脂肪酸水平差异及膳食补充n-3类脂肪酸对ADHD儿童体内脂肪酸水平的影响作用。方法在1 555名2~5年级学生中筛选出ADHD儿童79名,取50名非ADHD儿童作为对照,采集静脉血分析其脂肪酸差异。采用随机对照试验(RCT)原则,将ADHD儿童随机分为干预组和对照组,采用不同浓度的n-3多不饱和脂肪酸(PUFAs)膳食补充干预3个月,观察干预后脂代谢改善情况。结果ADHD儿童血红细胞膜的饱和脂肪酸(SFAs)中的C15∶0、C16∶0、C20∶0,单不饱和脂肪酸(MUFAs)中的C15∶1、C18∶1、C20∶1、C24∶1及PUFAs中的亚油酸C18∶2 n-6(LA)明显高于非ADHD组儿童(P0.05);花生四烯酸C20∶4 n-6(AA)、二十碳五烯酸C20∶5 n-3(EPA)及C22∶4(n-6)低于非ADHD组儿童。ADHD儿童补充n-3PUFAs后,体内α-亚麻酸C18∶3 n-3(ALA)、C24∶0、二十二碳六烯酸C22∶6 n-3(DHA)及n-3PUFAs水平显著提高,n-6PUFAs、n-6/n-3比例则显著降低。结论ADHD与非ADHD儿童体内的脂肪酸组成存在差异,补充n-3类脂肪酸可提高ADHD儿童体内n-3类脂肪酸水平,同时降低n-6/n-3比例。     

不同n-6/n-3脂肪酸构成对小鼠心血管疾病危险因素的影响

目的研究不同脂肪酸构成对小鼠血脂代谢、炎症和氧化应激及内皮细胞功能的影响。方法雄性KM小鼠随机分为5组,分别喂饲正常对照饲料、猪油高脂饲料和n-6/n-3多不饱和脂肪酸(PUFA)比值为1∶1、5∶1、20∶1的高脂饲料5周,比较各组小鼠血清中甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、白介素-6(IL-6)、丙二醛(MDA)、超敏C反应蛋白(hsCRP)、肿瘤坏死因子(TNF-α)、脂质过氧化物(LPO)、8-异前列腺素F2α(8-isoPGF2α)、氧化型低密度脂蛋白(ox-LDL)、游离脂肪酸(FFA)、选择素(ES)和血管性血友病因子(v WF)的含量变化。结果猪油组LDL-C和非高密度脂蛋白胆固醇(non-HDL-C)水平显著高于其他各组(P0.05)。n-6/n-3 PUFA 1∶1组和5∶1组血清TG、TC水平显著低于猪油组(P0.05)。20∶1组血清FFA水平显著高于1∶1组和5∶1组(P0.05)。1∶1组和5∶1组血清炎症因子和氧化应激指标及ES水平均显著低于猪油组和20∶1组(P0.05)。5∶1组血清v WF水平显著低于猪油组和20∶1组(P0.05)。结论与猪油和高n-6/n-3 PUFA比值高脂饲料相比较,低n-6/n-3PUFA比值高脂饲料可改善小鼠脂代谢、炎症与氧化应激和内皮细胞功能。     

不同n-3/n-6多不饱和脂肪酸构成比膳食对大鼠一磷酸腺苷活化蛋白激酶表达的影响

目的研究不同n-3/n-6配比脂肪酸对大鼠磷酸腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK)蛋白及活性表达的影响。方法58只SD大鼠适应性喂养7d后,尾静脉取血。根据血清总胆固醇水平随机分为:空白(基础饲料);高脂(高脂饲料);高脂1:1(高脂饲料+n-3/n-6=1:1配方油);高脂1:5(高脂饲料+n3/n6=1:5配方油);低脂1:1(脱脂基础饲料+n-3/n-6=1:1配方油);低脂1:5(脱脂基础饲料+n3/n6=1:5配方油)6组,喂养45d,观察大鼠摄食与体重增长。于实验前1d,15d,30d,45d分别各取血测血清总胆固醇水平,于D45处死动物。Western blotting分别分析肝和下丘脑组织中AMPK-α总蛋白及其活性表达。结果添加PUFA的4个比例组血清TC、体重与高脂组相比,显著降低,且低脂2个比例组和高脂1:1组均与高脂1:5组相比有显著差异。添加PUFA的4个比例组均与高脂组相比,大鼠下丘脑AMPK-α总蛋白表达水平明显降低,肝AMPK-α蛋白表达水平均比高脂组明显升高。结论PUFA改善血脂可能是通过增加肝AMPK表达,抑制下丘脑AMPK表达,增加肝脂肪酸氧化和抑制食欲,影响血脂代谢。     

杭州地区男性素食者细胞免疫水平与血浆磷脂脂肪酸构成的相关性

目的研究杭州地区男性素食者细胞免疫功能水平及其与血浆磷脂脂肪酸的相关性。方法采用流式细胞术测定89例男性素食者(素食组)和103例健康体检者(对照组)的外周血淋巴细胞亚群,采用气相色谱法测定血浆磷脂脂肪酸的构成。结果与对照组相比,素食组CD3+T淋巴细胞、CD4+T淋巴细胞、CD8+T淋巴细胞、CD16+/56+自然杀伤(NK)细胞百分比及CD4+/CD8+比值均无统计学意义,而素食者CD19+B淋巴细胞低于对照组,差异有非常显著意义(P<0.01)。相关性分析显示,CD3+T淋巴细胞和CD4+T淋巴细胞均与血浆n-3多不饱和脂肪酸(polyunsaturated fatty acids,PUFAs)含量存在负相关(P<0.01),CD19+B淋巴细胞与n-6 PUFAs部分指标存在负相关(P<0.05),NK细胞与n-3 PUFA部分存在正相关(P<0.01),但与总n-3 PUFAs及n-6 PUFAs均无相关性。结论素食者的细胞免疫功能水平无改变,体液免疫功能水平下降,部分原因与血浆磷脂脂肪酸构成变化有关。     

广州成人膳食n-6/n-3脂肪酸比值与心血管疾病危险因素的关系

目的分析广州40～65岁居民膳食n-6/n-3脂肪酸比值与心血管疾病危险因素的关系。方法 40～65岁广州市民1133人,采用定量食物频数问卷调查对象的每日摄入食物种类和数量,计算能量和营养素摄入量,检测其红细胞膜脂肪酸构成、血脂及颈动脉内中膜厚度(IMT),分析n-6/n-3比值大小高Q3,中Q2,低Q1与血压、血脂和IMT的关系。结果 995人资料完整纳入分析。对象日均膳食总能量摄入为9.10±2.09MJ、脂肪供能比为(34.3±7.9)%。膳食n-6/n-3脂肪酸比值为(29.74±22.71):1,红细胞膜n-6/n-3脂肪酸比值为(2.7±1.0):1,膳食SFA:MUFA:PUFA为1:1.5:1。膳食n-3脂肪酸摄入量与红细胞膜n-3构成比、膳食n-6/n-3比值与红细胞膜n-6/n-3比值均呈显著正相关关系。膳食n-6/n-3比值最高组Q3(>31.16)对象的收缩压、TC和IMT水平显著高于最低组Q1(<17.40);红细胞膜n-6/n-3比值最高组Q3(>3.04)和中间组Q2(2.18～3.03)对象的收缩压、舒张压、TC、LDL-C及IMT水平均显著高于最低组Q1(≤2.17)。结论广州市40～65岁居民膳食n-6/n-3脂肪酸比值约为30:1;该比值小于17.40:1时,有较低的血压,总胆固醇及IMT水平。     

不同脂肪酸构成比对小鼠血脂影响的实验研究

目的:以小鼠饲料正常脂肪摄入量7.84%为基础,比较不同脂肪酸构成比对小鼠血脂水平的影响。方法:以小鼠正常饲料脂肪及脂肪酸构成为对照,分别设S/M/P比值为1∶1.7∶1.2和1∶1∶1的饲料,其中n-6/n-3比值在1～10∶1各设计4组,共10组, 喂小鼠10 w,测定血脂水平。结果: S/M/P为1∶1.7∶1.2, n-6/n-3在1～5∶1时TC和TC/HDL-C水平显著低于8∶1和10∶1组(P<0.05); S/M/P为1∶1∶1,n-6/n-3为1∶1时的TC和LDL-C水平显著低于其余各比值组(P<0.05);当n-6/n-3为10∶1时,S/M/P为1∶1.7∶1.2的TC、LDL-C、HDL-C以及TC/HDL-C和LDL-C/HDL-C水平均显著低于1∶1∶2组(P<0.05),S/M/P为1∶1∶2的LDL-C和TC/HDL-C水平显著低于1∶1∶1组(P<0.05)。结论: S/M/P现状1∶1.7∶1.2时,n-6/n-3在1～5∶1可维持血脂在较低水平;如脂肪酸构成比为1∶1∶1时,维持较低血脂所需的n-6/n-3为1∶1;在现状膳食n-6/n-3为10∶1时,S/M/P在1∶1.7∶1.2有利于维持低血脂。     

孕期及哺乳期n-6/n-3脂肪酸变化对仔鼠脑发育相关基因表达的影响

目的探讨孕及哺乳期摄入n-6/n-3多不饱和脂肪酸(PUFAs)变化对子代脑功能相关基因表达的影响。方法选用清洁级3～4周龄C57BL/6J雌性小鼠,随机分成5组,每组分别给予n-3 PUFAs缺乏和4种不同含量n-3 PUFAs(n-6/n-3 PUFAs比值分别为15∶1、5∶1、1∶1及1∶5)饲料喂养。小鼠12～14周龄时用常规饲料喂养的雄性小鼠与之合笼交配繁殖,仔鼠断乳后继续行母鼠相同饲料喂养,随访观察至生后7d、21d和12周龄时分批处死后取脑。然后在仔鼠生后21d断乳时,随机挑选7～9只n-3 PUFAs缺乏组的仔鼠用n-6/n-3 PUFAs(5∶1)组饲料喂养,至12周龄;同时随机挑选7～9只n-6/n-3 PUFAs(5∶1)组的仔鼠,改用n-3缺乏组饲料喂养,至12周龄;剩余仔鼠用与母鼠相同的饲料喂养,至12周龄;麻醉牺牲后,取脑置于-80℃条件下备用。采用实时荧光定量PCR技术测定脑皮质gfap、mbp、nse和nr2b基因mRNA的表达。结果在各年龄段小鼠中,饲料中添加n-3 PUFAs使各基因的表达量明显增加;不同比例的n-6/n-3PUFAs对基因表达的影响不同。孕期及哺乳期饲料缺乏n-3 PUFAs,即使断乳后的饲料中添加正常量的n-3 PUFAs,也不能使某些对脑功能起重要作用的基因的表达量升高至正常n-3 PUFAs喂养的小鼠。结果提示,孕期及哺乳期可能需要较高的n-3 PUFAs摄入(可能最优的n-6/n-3 PUFAs比例介于1∶5～1∶1之间),才能满足幼年期脑发育之需。结论孕及哺乳期n-3多不饱和脂肪酸(PUFAs)的适量摄入,有助于维持成年期脑功能相关基因的正常表达。     

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。     

饲料n-3多不饱和脂肪酸含量对仔鼠脑神经元、胶质细胞和髓鞘发育的影响

【目的】探讨孕期及哺乳期饲料中n-3多不饱和脂肪酸(polyunsaturated fatty acids,PUFAs)含量变化对仔鼠脑组织结构的影响。【方法】使用6~8周龄清洁级C57BL/6J雌性小鼠,分别给予4种不同含量的鱼油n-3 PU-FAs(n-6/n-3 PUFAs比值分别为20∶1、10∶1、5∶1和1∶1)饲料和1种亚麻油n∶3 PUFAs饲料(n∶6/n∶3 PUFAs比值为1∶1)喂养6周;以n∶3 PUFAs缺乏饲料为对照。小鼠饲养至12~14周龄时雌雄合笼交配繁殖,新生仔鼠21日龄断乳时处死,取脑进行组织固定。采用免疫组织化学技术对脑组织神经特异性烯醇化酶(neuron specific enolase,NSE)、胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)、髓鞘碱性蛋白(myelin basic protein,MBP)进行分析。【结果】与n∶3 PU-FAs缺乏组相比,n∶3 PUFAs饲料喂养组小鼠脑皮质30区及海马CA3区NSE阳性细胞平均光密度、海马CA1区GFAP阳性细胞平均光密度及面数密度、胼胝体及海马纤维MBP平均光密度均显著增加。上述指标在n-6/n-3 PUFAs(5∶1)和(1∶1)组之间未存在差异,但均显著高于(10∶1)和(20∶1)组。与亚麻油n-3 PUFAs饲料组相比,上述指标在n-6/n-3 PU-FAs(1∶1)鱼油饲料组明显升高。【结论】需要摄入较高含量的n-3 PUFAs(n-6/n-3 PUFAs比例在5∶1以下)才能更好地满足脑神经元、星形胶质细胞及髓鞘的发育需求;亚麻油来源的亚麻酸不如鱼油中的二十二碳六烯酸效果好。     

Lack of effect of dietary n-6:n-3 PUFA ratio on plasma lipids and markers of insulin responses in Indian Asians living in the UK

Summary Background Indian Asians living in Western Countries have an over 50 % increased risk of coronary heart disease (CHD) relative to their Caucasians counterparts. The atherogenic lipoprotein phenotype (ALP), which is more prevalent in this ethnic group, may in part explain the increased risk. A low dietary long chain n-3 fatty acid (LC n-3 PUFA) intake and a high dietary n-6 PUFA intake and n-6:n-3 PUFA ratio in Indian Asians have been proposed as contributors to the increased ALP incidence and CHD risk in this subgroup. Aim To examine the impact of dietary n-6:n-3 PUFA ratio on membrane fatty acid composition, blood lipid levels and markers of insulin sensitivity in Indian Asians living in the UK. Methods Twentynine males were assigned to either a moderate or high n-6:n-3 PUFA (9 or 16) diet for 6 weeks. Fasting blood samples were collected at baseline and 6 weeks for analysis of triglycerides, total-, LDL- and HDL-cholesterol, non-esterified fatty acids, glucose, insulin, markers of insulin sensitivity and C-reactive protein. Results Group mean saturated fatty acid, MUFA, n-6 PUFA and n-3 PUFA on the moderate and high n-6:n-3 PUFA diets were 26 g/d, 43 g/d, 15 g/d, 2 g/d and 25 g/d, 25 g/d, 28 g/d, 2 g/d respectively. A significantly lower total membrane n-3 PUFA and a trend towards lower EPA and DHA levels were observed following the high n-6:n-3 PUFA diet. However no significant effect of treatment on plasma lipids was evident. There was a trend towards a loss of insulin sensitivity on the high n-6:n- 3 PUFA diet, with the increase in fasting insulin (P = 0.04) and HOMA IR [(insulin x glucose)/ 22.5] (P = 0.02) reaching significance. Conclusion The results of the current study suggest that, within the context of a western diet, it is unlikely that dietary n-6:n-3 PUFA ratio has any major impact on the levels of LC n-3 PUFA in membrane phospholipids or have any major clinically relevant impact on insulin sensitivity and its associated dyslipidaemia. Source of support: This project was funded by the Food Standards Agency (FSA), UK.     

Effect of increasing the dietary (n-3) to (n-6) polyunsaturated fatty acid ratio on murine liver and peritoneal cell fatty acids and eicosanoid formation

An incremental increase in the dietary (n-3):(n-6) polyunsaturated fatty acid (PUFA) ratio from 0 to 1.93 in diets containing 15% fat (wt/wt) decreased the total (n-6) PUFA content of phospholipids of the liver and peritoneal cells (macrophage) in mice from 43.1 and 33.6 mol/100 mol to 16.0 and 12.3 mol/100 mol with a concomitant increase of 27.6 and 16.1 mol/100 mol in (n-3) PUFA, respectively. Consumption of (n-3) PUFA increased hepatic (n-3) PUFA levels without changing total PUFA (46.35 vs. 46.87 mol/100 mol), whereas macrophage PUFA levels were decreased. The synthesis of sulfidopeptide leukotrienes (SP-LT) (LTC4 and LTE4) was progressively reduced by increasing dietary (n-3) PUFA, i.e., there was a reduction of 76% in mice fed a diet containing a (n-3):(n-6) PUFA ratio of 1.93 compared with the control diet. The 5-series SP-LT (LTC5 and LTF5) were produced in all animals consuming (n-3) PUFA and accounted for 62% of all SP-LT synthesized in mice fed the diet containing a 1.93 (n-3):(n-6) PUFA ratio. Synthesis of 6-keto-prostaglandin F1 alpha decreased 81% in mice fed a diet containing a (n-3):(n-6) PUFA ratio of 1.93 whereas prostaglandin E2 synthesis decreased 44% in mice fed diets with (n-3):(n-6) ratios ranging from 0.41 to 1.93.     

Dietary (n-3) polyunsaturated fatty acids modulate murine Th1/Th2 balance toward the Th2 pole by suppression of Th1 development

We showed that dietary long-chain (n-3) PUFAs present in fish oil (FO) affect CD4(+) T cell proliferation and cytokine production in C57BL/6 mice. To test the hypothesis that the anti-inflammatory effect of dietary (n-3) PUFAs could be due to the indirect suppression of T helper (Th)1 cells by cross-regulation of enhanced Th2 activation, mice were fed a wash-out control diet [5% corn oil (CO), (n-6) PUFA] for 1 wk, followed by the control diet or a fish oil diet [1% CO + 4% FO, (n-3) PUFA] for 2 wk. Splenic CD4+ T cells were cultured under both neutral and Th2 polarizing conditions for 2 d. Cells were reactivated and analyzed for interleukin-4 and interferon-gamma by intracellular cytokine staining. Dietary fish oil significantly increased the percentage of Th2 polarized cells and suppressed Th1 cell frequency under neutral conditions. However, under Th2 polarizing conditions, although the suppression of Th1 cells was maintained in FO-fed mice, no effect was observed in Th2 cells. Dietary fish oil increased the Th2/Th1 ratio in the presence of homologous mouse serum under both neutral (P = 0.0009) and Th2 polarizing conditions (P = 0.0185). The FO diet did not significantly affect proliferation under Th2 polarizing conditions. Thus, the anti-inflammatory effects of FO may be explained in part by a shift in the Th1/Th2 balance, due to the direct suppression of Th1 development, and not by enhancement of the propensity of CD4+ T cells to be polarized toward a Th2 phenotype, at least in vitro.     

Lower eicosapentaenoic acid and higher arachidonic acid levels in Sera of young adults in the Netherlands than in Japan

To survey risk factors in coronary heart disease, we compared serum fatty acid composition and lipids for university students in Japan (33 males and 29 females) and in the Netherlands (20 males and 19 females). No significant differences were found between the mean levels of cholesterol (Chol) and triglycerides (TG) between the subjects in the two countries. The mean levels of polyunsaturated fatty acid (PUFA), monounsaturated fatty acid (MUFA) and saturated fatty acid (SFA) of Japanese students were similar to those of the Dutch students. In both countries, the levels of Chol showed a positive correlation with the levels of PUFA, n-6 PUFA, linoleic acid (C18:2n-6), and arachidonic acid (AA, C20:4n-6) but no correlation with the percentages of PUFA and the ratio of PUFA/SFA. On the other hand, the TG levels correlated inversely with the percentage of PUFA and the ratios of PUFA/SFA in both countries. When compared to those of Japanese students, low eicosapentaenoic acid (EPA, C20:5n-3) and high AA were found in the Dutch students (p < 0.001, respectively). The total amounts of n-3 PUFA in the Dutch were significandy lower than those in the Japanese (p < 0.001) but no differences among those of n-6 PUFA. The ratios of EPA/AA and n-3/n-6 PUFA of the Dutch students were lower than those of the Japanese students (p < 0.001, respectively). The ratio of EPA/AA showed a positive correlation with EPA but not with AA in both countries. The levels of Toc which will decrease the risk of coronary vascular disease (CVD) were lower in Japan than those in the Dutch in both sexes (p < 0.01, respectively). These results suggest that the low EPA and high AA levels and the low n-3/n-6 PUFA ratio may lead to greater incidence of CVD.     

Protective effect of dietary n-3 polyunsaturated fatty acids on myocardial resistance to ischemia-reperfusion injury in rats

Dietary n-3 polyunsaturated fatty acids (PUFA) reduce coronary heart disease (CHD) complications, such as chronic arrhythmia and sudden cardiac death. Improved myocardial resistance to ischemia-reperfusion injury results in smaller myocardial infarction, which is a major factor in the occurrence of CHD complications. We hypothesized that a specific dietary fatty acid profile (low in saturated and n-6 PUFA but high in plant and marine n-3 PUFA) may improve myocardial resistance to ischemia-reperfusion injury and reduce infarct size. To test this assumption, we used a well-defined rat model of myocardial infarction. Based on our results, in comparison to a diet that is high in either saturated or n-6 PUFA but poor in plant and marine n-3 PUFA, a diet that is low in saturated fats and n-6 PUFA but rich in plant and marine n-3 PUFA results in smaller myocardial infarct size (P < .01). The effects of the 3 diets were also examined by analyzing the fatty acid composition of plasma, erythrocyte cell membranes, and the phospholipids of myocardial mitochondria. The results show a great accumulation of n-3 PUFA and a parallel decrease in arachidonic acid, the main n-6 PUFA, in plasma, cell membranes, and cardiac mitochondria (P < .0001). We conclude that improved myocardial resistance to ischemia-reperfusion may be one of the critical factors explaining the protective effects of dietary n-3 PUFA against CHD complications in humans. In addition to increasing n-3 PUFA intake, an optimal dietary pattern aimed at reducing cardiovascular mortality should include a reduction of the intake of both saturated and n-6 PUFA.     

Anti-inflammatory and anti-angiogenic effect of long chain n-3 polyunsaturated fatty acids in intestinal microvascular endothelium

Background & aims

The role of endothelial cells in inflammatory bowel disease has been recently emphasized. Endothelial activation and expression of adhesion molecules are critical for leukocytes recruitment into the inflammatory wall. Compelling evidence demonstrated anti-inflammatory effects of long chain n-3 PUFA in inflammatory models. We previously showed that long chain n-3 PUFA (EPA and DHA) inhibited inflammatory response in epithelial and dendritic cells. As long chain n-3 PUFA treatment led to a decreased expression of adhesion molecules in endothelial cells from other organs, we have now investigated their effect on intestinal endothelial cells in vitro and in colitic rats.

Methods

In vitro study: Primary culture of human intestinal microvascular endothelial cells (HIMEC) were pre-treated with DHA and then incubated with IL-1β. In vivo study: Colitis was induced in 2 groups at day0 by intrarectal injection of 2-4-6-trinitrobenzen sulfonic acid (TNBS). Rats received by gavage either fish oil, rich in EPA and DHA (TNBS+n-3) or an isocaloric isolipidic oil formula for 14 days.

Results

DHA led to a decreased VCAM-1, TLR4, cyclooxygenase-2 and VEGFR2 expression and a decreased production of IL-6, IL-8 and GM-CSF and a reduced production of PGE₂ and LTB₄ (p < 0.001) in IL-1β-induced HIMEC. Similarly, dietary intervention with fish oil rich in EPA and DHA significantly decreased colon production of PGE₂ and LTB_4, endothelial VCAM-1 and VEGFR2 in rats with colitis.

Conclusions

Data obtained from in vitro and in vivo studies reveal a potential anti-angiogenic role of long chain n-3 PUFA in intestinal endothelial cells. This protective effect of long chain n-3 PUFA may partly explain the observed benefit of dietary intake of long chain n-3 PUFA in IBD development.     

Dietary ratio of (n-6)/(n-3) polyunsaturated fatty acids alters the fatty acid composition of bone compartments and biomarkers of bone formation in rats

The effects of dietary polyunsaturated fatty acids (PUFA) on ex vivo bone prostaglandin E(2) (PGE(2)) production and bone formation rate were evaluated in rats. Weanling male Sprague-Dawley rats were fed AIN-93G diet containing 70 g/kg of added fat for 42 d. The dietary lipid treatments were formulated with safflower oil and menhaden oil to provide the following ratios of (n-6)/(n-3) fatty acids: 23.8 (SMI), 9.8 (SMII), 2.6 (SMIII), and 1.2 (SMIV). Ex vivo PGE(2) production in liver homogenates and bone organ cultures (right femur and tibia) were significantly lower in rats fed diets with a lower dietary ratio of (n-6)/(n-3) fatty acids than in those fed diets with a higher dietary ratio. Regression analysis revealed a significant positive correlation between bone PGE(2) and the ratio of arachidonic acid (AA)/eicosapentaenoic acid (EPA), but significant negative correlations between bone formation rate and either the ratio of AA/EPA or PGE(2) in bone. Activities of serum alkaline phosphatase isoenzymes, including the bone-specific isoenzyme (BALP), were greater in rats fed a diet high in (n-3) or a low ratio of (n-6)/(n-3), further supporting the positive action of (n-3) fatty acids on bone formation. These results demonstrated that the dietary ratio of (n-6)/(n-3) modulates bone PGE(2) production and the activity of serum BALP in growing rats.