n-3多不饱和脂肪酸与2型糖尿病关系的研究进展

综述了n-3多不饱和脂肪酸是否可以减少或延缓健康人群发生糖尿病及其血管并发症的风险,以及2型糖尿病患者中外源性n-3多不饱和脂肪酸的摄入是否可以改善胰岛素抵抗和降低心血管疾病并发症的发生发展的临床研究进展,从而探索其在医学营养治疗学中的应用价值。     

n-6/n-3多不饱和脂肪酸比例对机体生理功能的调节

多不饱和脂肪酸(Polyunsaturated fatty acids,PUFA),尤其是n-6和n-3 PUFAs,不仅是人体必需营养素,在调节和预防人类疾病方面同时发挥着重要作用。n-6和n-3 PUFAs在哺乳动物细胞内不能相互转换,且是动植物细胞膜的重要组成成分,具有不同的生理功能。细胞膜多不饱和脂肪酸组成比例很大程度上由膳食决定,因此平衡膳食中n-6/n-3 PUFAs具有重要意义。本文总结了n-6和n-3 PUFAs的代谢途径和作用机制,结合临床试验,阐述了平衡n-6/n-3 PUFA的重要性。     

n-3多不饱和脂肪酸改善糖脂代谢的研究进展

糖脂代谢的稳态调控是维持机体基本生命活动的基础,糖脂代谢的紊乱与糖尿病、肥胖、脂肪肝、心血管疾病及细胞异常增殖的发生和发展密切相关。富含生物活性n-3多不饱和脂肪酸的鱼油具有调控糖脂代谢紊乱的功能,然而其作用是复杂多方面的,目前对其靶点和分子作用机制的理解尚不全面。本文结合近年来国内外的最新研究进展,综述了n-3多不饱和脂肪酸对生物体糖代谢和脂代谢的影响。     

n-3PUFA调节脂代谢机制的研究进展

日粮中的n-3PUFA具有多种作用,除了调节质膜组成和影响细胞信号之外,同时还涉及多 种与脂代谢有关酶与蛋白的基因表达,如:PPARα、SREBPs、LXR等,通过它们来影响靶基因(如: ACO-A、FAS等)的表达,从而起到调控脂肪沉积的作用。     

膳食中高n-6/n-3多不饱和脂肪酸比值对小鼠肠道菌群的影响

目的:探讨小鼠膳食中高n-6/n-3多不饱和脂肪酸比值对肠道菌群的影响。方法:随机选取健康的30只C57/B6小鼠分为对照组(基础饲料)、花生四烯酸组(基础饲料+10%花生四烯酸)、鱼油组(基础饲料+10%鱼油)。喂食16周,16周后提取小鼠肠道菌群宏基因组DNA,采用Roche 454测序技术对肠道菌群16Sr RNA基因V3-V5区域进行测序,对菌群的组成结构以及含量的变化进行分析。结果:花生四烯酸组小鼠体内厚壁菌门的含量达到(55.3±5.26)%,与对照组小鼠体内厚壁菌门的含量(30.23±8.75)%相比显著性升高(P0.05)。并且花生四烯酸组小鼠体内变形菌门的含量(3±0.762)%与对照组(1.5±0.265)%相比也显著性上升(P0.05)。结论:膳食中高n-6/n-3多不饱和脂肪酸比值会造成小鼠体内肠道菌群组成结构的失衡,导致厚壁菌门以及变形菌门的含量上升。     

n-3脂肪酸代谢产物抗炎作用的研究进展

炎症反应是机体正常组织对感染和损伤的应答,然而过度的炎症反应往往会引起急性和慢性疾病的发生.最近研究发现,由n-3多不饱和脂肪酸二十碳五烯酸和二十二碳六烯酸代谢产生的resolvins和protectins两类化合物,具有很强的抗炎和炎症修复活性.综述了resolvins和protectin D1的来源、抗炎作用和抗炎机制,为进一步开展n-3多不饱和脂肪酸及其代谢产物的抗炎作用研究、为炎症的防治提供新的思路.     

n-3多不饱和脂肪酸对2型糖尿病患者血脂及炎症因子的影响

【摘要】 目的 ①观察不同成分的n-3PUFA对2型糖尿病患者血脂水平的影响;②观察不同成分的n-3PUFA对2型糖尿病患者C反应蛋白和白介素-6的影响。方法采用随机双盲对照方法,将108例2型糖尿病患者随机分为3组,分别服用含有不同成分（ALA、EPA、DHA)的 n-3PUFA胶囊4g/d,观察时间为6个月,A组（金枪鱼油组,胶囊成分n-3PUFA-DHA+EPA）,B组（亚麻籽油组,胶囊成分为n-3PUFA-ALA）,C组（玉米油组,对照组）。分别在基线、3个月、6个月时检测血脂、白介素-6和C反应蛋白等实验数据,进行统计学分析。结果①组内比较： A组在3月时HDL较治疗前升高,其差异具有统计学意义（p<0.05）,6月时具有显著统计学差异（p<0.01）;6月时,TC水平较治疗前降低,其差异具有统计学意义（p<0.05）;B组和C组3月、6月时,血脂无明显变化（均p>0.05）。组间比较：3月时,三组患者血脂水平均无显著差异（均p>0.05）;6月时A组和C组之间HDL水平差异具有统计学意义（p<0.05）。②组内比较：A组CRP和IL-6水平在3月时均较治疗前降低,其差异具有统计学意义（p<0.05）,6月时具有显著统计学差异（p<0.01）;B组和C组3月、6月时,CRP和IL-6水平无明显变化（均p>0.05）。组间比较：3月时,三组CRP和IL-6水平均无显著差异（均p>0.05）;6月时A组和C组之间CRP和IL-6水平差异具有统计学意义（p<0.05）。 结论 ①服用n-3PUFA（金枪鱼油,胶囊成分n-3PUFA-DHA+EPA ）4g/d可以升高2型糖尿病患者高密度脂蛋白,同时降低总胆固醇水平;②服用n-3PUFA（金枪鱼油,胶囊成分n-3PUFA-DHA+EPA ）4g/d可以降低糖尿病患者C反应蛋白和白介素-6水平。     

△6-脂肪酸脱氢酶对n-6和n-3途径中脂肪酸底物的偏好

添加α-亚麻酸作为底物,经半乳糖诱导,在含有少根根霉△6-脂肪酸脱氢酶基因的酿酒酵母总脂肪酸中检测到十八碳四烯酸的生成;同时添加亚油酸和α-亚麻酸时,检测到γ-亚麻酸和十八碳四烯酸生成,而且十八碳四烯酸的含量是γ-亚麻酸含量的3.81倍,表明在酿酒酵母中少根根霉△6-脂肪酸脱氢酶不仅能催化α-亚麻酸生成十八碳四烯酸,而且偏好n-3途径中的底物α-亚麻酸.同样,在改变少根根霉△6-脂肪酸脱氢酶基因的转译起始密码子周边序列后所构建的转基因酵母中,也得到类似的结果,而且各种目的脂肪酸的含量均有明显提高.     

Δ^6-脂肪酸脱氢酶对n-6和n-3途径中脂肪酸底物的偏好

添加α-亚麻酸作为底物,经半乳糖诱导,在含有少根根霉Δ^6-脂肪酸脱氢酶基因的酿酒酵母总脂肪酸中检测到十八碳四烯酸的生成;同时添加亚油酸和α-亚麻酸时,检测到γ-亚麻酸和十八碳四烯酸生成,而且十八碳四烯酸的含量是γ-亚麻酸含量的3．81倍,表明在酿酒酵母中少根根霉Δ^6-脂肪酸脱氢酶不仅能催化α-亚麻酸生成十八碳四烯酸,而且偏好n-3途径中的底物α-亚麻酸。同样,在改变少根根霉Δ^6-脂肪酸脱氢酶基因的转译起始密码子周边序列后所构建的转基因酵母,也得到类似的结果,而且各种目的脂肪酸的含量均有明显提高。     

Δ~6-脂肪酸脱氢酶对n-6和n-3途径中脂肪酸底物的偏好

添加α 亚麻酸作为底物 ,经半乳糖诱导 ,在含有少根根霉Δ6 脂肪酸脱氢酶基因的酿酒酵母总脂肪酸中检测到十八碳四烯酸的生成 ;同时添加亚油酸和α 亚麻酸时 ,检测到γ 亚麻酸和十八碳四烯酸生成 ,而且十八碳四烯酸的含量是γ 亚麻酸含量的 3 81倍 ,表明在酿酒酵母中少根根霉Δ6 脂肪酸脱氢酶不仅能催化α 亚麻酸生成十八碳四烯酸 ,而且偏好n 3途径中的底物α 亚麻酸。同样 ,在改变少根根霉Δ6 脂肪酸脱氢酶基因的转译起始密码子周边序列后所构建的转基因酵母中 ,也得到类似的结果 ,而且各种目的脂肪酸的含量均有明显提高     

n-3、n-6PUFA高脂饮食对SD大鼠肝脏胆固醇合成相关基因表达影响

目的探讨n-3、n-6多不饱和脂肪酸(PUFA)高脂饮食对SD大鼠肝脏Srebp2及Hmgcr表达的影响。方法 SD大鼠随机分为3组,分别为对照组(NC)、n-3 PUFA组(TUF)及n-6 PUFA组(SUF),8周后测量血清总胆固醇(TCH)水平,实时定量PCR检测Srebp2及Hmgcr基因表达,Western blotting检测SREBP2及HMGCR蛋白表达。结果 TUF组、SUF组血清TCH含量均显著降低(P<0.001),TUF组最低。TUF组、SUF组Srebp2及Hmgcr基因表达水平均显著增高(P=0.007,P=0.012),SUF组Srebp2最高,TUF组Hmgcr最高。TUF组HMGCR蛋白表达显著高于NC组及SUF组,SUF组与NC组差异无显著性;三组SREBP2蛋白表达。结论 n-3、n-6PUFA降低血清胆固醇不是通过抑制Srebp2及Hmgcr表达实现的。     

Δ-6 Desaturase Substrate Competition: Dietary Linoleic Acid (18∶2n-6) Has Only Trivial Effects on α-Linolenic Acid (18∶3n-3) Bioconversion in the Teleost Rainbow Trout

It is generally accepted that, in vertebrates, omega-3 (n-3) and omega-6 (n-6) poly-unsaturated fatty acids (PUFA) compete for Δ-6 desaturase enzyme in order to be bioconverted into long-chain PUFA (LC-PUFA). However, recent studies into teleost fatty acid metabolism suggest that these metabolic processes may not conform entirely to what has been previously observed in mammals and other animal models. Recent work on rainbow trout has led us to question specifically if linoleic acid (LA, 18∶2n-6) and α-linolenic acid (ALA, 18∶3n-3) (Δ-6 desaturase substrates) are in direct competition for access to Δ-6 desaturase. Two experimental diets were formulated with fixed levels of ALA, while LA levels were varied (high and low) to examine if increased availability of LA would result in decreased bioconversion of ALA to its LC-PUFA products through substrate competition. No significant difference in ALA metabolism towards n-3 LC-PUFA was exhibited between diets while significant differences were observed in LA metabolism towards n-6 LC-PUFA. These results are evidence for minor if any competition between substrates for Δ-6 desaturase, suggesting that, paradoxically, the activity of Δ-6 desaturase on n-3 and n-6 substrates is independent. These results call for a paradigm shift in the way we approach teleost fatty acid metabolism. The findings are also important with regard to diet formulation in the aquaculture industry as they indicate that there should be no concern for possible substrate competition between 18∶3n-3 and 18∶2n-6, when aiming at increased n-3 LC-PUFA bioconversion in vivo.     

Higher plasma n-3 fatty acid status in the moderately healthy elderly in southern Québec: Higher fish intake or aging-related change in n-3 fatty acid metabolism?

The elderly reportedly have a significantly higher % of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids in plasma and red cell lipids. However, these observations are from a few small studies and the health status of the elderly in these studies is for the most part unclear. Since the elderly are susceptible to cardiovascular and neurological illnesses that seem to be related in part to lower intake of n-3 fatty acids it seems paradoxical that their blood levels of EPA and DHA would be higher than in young adults. We report here plasma fatty acid profiles and their response to supplementation with two types of fish oils from several of our recent studies in the moderately healthy elderly. We define the moderately healthy elderly as those who were in good physical condition, had no cognitive decline and, if present, in whom hypothyroidism, hyperlipidemia and/or hypertension were well-controlled. As shown previously, we confirm the higher % EPA and % total n-3 fatty acids (but not DHA) in fasting plasma and extend these findings to include higher plasma concentrations (mg/L) of n-3 fatty acids as well. The EPA-predominant supplement raised DHA only in the young, whereas the DHA-predominant supplement raised EPA more in the young than in the elderly. The moderately healthy elderly clearly have higher plasma n-3 fatty acids but whether this reflects differences in intake versus aging-related changes in n-3 fatty acid metabolism remains to be elucidated.     

n-3多不饱和脂肪酸调节饮食诱导肥胖大鼠miRNA表达变化

目的：研究n-3多不饱和脂肪酸（polyunsaturated fatty acids,PUFA）饮食对饮食诱导肥胖大鼠的miR NA表达影响。方法：将10只饮食诱导肥胖（diet induced obese,DIO）大鼠随机分成两组：n-3PUFA添加组和安慰剂添加组（对照组）;每周记录两组老鼠的体重、体长和进食量。对外周血miR NA的表达并进行分析和预测。结果：两组老鼠Lee指数有统计学差异（P〈0.05）;与对照组相比,在n-3组的外周血单核细胞中,29个miR NA上调,31个下调;其中rno-miR-200和rno-miR-211的表达量上调,rno-miR-29b和rno-miR-92b的表达量下调,其靶基因预测结果与神经营养因子,脂肪细胞因子,趋化因子和胰岛素信号通路有关。结论：n-3PUFA能够调节DIO大鼠的miR NA水平,其中有些与脂肪代谢相关。     

Fat-1基因在n-3多不饱和脂肪酸功能研究中的应用

n-3多不饱和脂肪酸是机体脂肪酸成分之一,维持体内合理的n-3多不饱和脂肪酸比例具有重要的生理意义。但n-3多不饱和脂肪酸在大多数动物体内不能合成,只能从食物中补充。fat-1基因的出现改变了这一现状,它可以将多不饱和脂肪酸从n-6形式转化为n-3形式。文章综述了n-3多不饱和脂肪酸的功能,并介绍了fat-1基因的功能及转fat-1基因动物在n-3多不饱和脂肪酸功能研究上的应用。     

Dietary n-6- or n-3-rich vegetable fats and α-tocopheryl acetate: effects on fatty acid composition and stability of rabbit plasma, liver and meat

We supplemented diets with α-tocopheryl acetate (100 mg/kg) and replaced beef tallow (BT) in feeds with increasing doses of n-6- or n-3-rich vegetable fat sources (linseed and sunflower oil), and studied the effects on the fatty acid (FA) composition, the α-tocopherol (αT) content and the oxidative stability of rabbit plasma and liver. These effects were compared with those observed in a previous study in rabbit meat. As in meat, the content of saturated, monounsaturated and trans FA in plasma and liver mainly reflected feed FA profile, except stearic acid in liver, which increased as feeds contained higher doses of vegetable fat, which could be related to an inhibition of the activity of the stearoyl-CoA-desaturase. As linseed oil increased in feeds, the n-6/n-3 FA ratio was decreased in plasma and liver as a result of the incorporation of FA from diets and also, due to the different performance and selectivity of desaturase enzymes. However, an increase in the dose of vegetable fat in feeds led to a significant reduction in the αT content of plasma and liver, which was greater when the fat source was linseed oil. Increasing the dose of vegetable fat in feeds also led to an increase in the susceptibility to oxidation (lipid hydroperoxide (LHP) value) of rabbit plasma, liver and meat and on the thiobarbituric acid (TBA) values of meat. Although the dietary supplementation with α-tocopheryl acetate increased the αT content in plasma and liver, it did not modify significantly their TBA or LHP values. In meat however, both TBA and LHP values were reduced by the dietary supplementation with α-tocopheryl acetate. The plasma αT content reflected the αT content in tissues, and correlated negatively with tissue oxidability. From the studied diets, those containing 1.5% linseed oil plus 1.5% BT and 100 mg of α-tocopheryl acetate/kg most improved the FA composition and the oxidative stability of rabbit tissues.     

Reversal of high-fat diet-induced hepatic steatosis by n-3 LCPUFA: role of PPAR-α and SREBP-1c

Nonalcoholic fatty liver disease is characterized by an abnormal accumulation of triacylglycerides in the liver in absence of significant alcohol consumption. Under these conditions, it has been observed an impaired bioavailability of hepatic n-3 long-chain polyunsaturated fatty acids (LCPUFAs). The aim of this study was to test the reversion of the prosteatotic and proinflammatory effects of high-fat diet (HFD) in the mouse liver by changing to normocaloric diet and n-3 LCPUFA supplementation. Male C57BL/6J mice were given either control diet (CD) or HFD for 12 weeks. Control and HFD groups were divided into subgroups that continue with CD or subjected to CD plus n-3 LCPUFA for 8 additional weeks. After this time, blood and liver samples were taken and metabolic, morphologic, oxidative stress, inflammatory and signaling parameters were analyzed. The dietary change from HFD to a normocaloric diet with n-3 LCPUFA supplementation significantly reduced insulin resistance and liver steatosis when compared to switching HFD to normocaloric diet alone. In addition, HFD-induced increases in adiposity, adipocyte enlargement and liver oxidative stress and inflammatory cytokine expression were suppressed by n-3 LCPUFA to control values. Importantly, n-3 LCPUFA supplementation abolish HFD-induced enhancement in hepatic SREBP-1c/PPAR-α ratios, suggesting a change in the metabolic status of the liver from a lipogenic condition to one favoring fatty acid oxidation and steatosis attenuation. These findings may provide the rational basis for the use of normocaloric diets supplemented with n-3 LCPUFA in patients with liver steatosis.     

Interaction of Sesamin and Eicosapentaenoic Acid against Δ5 Desaturation and n-6/ n-3 Ratio of Essential Fatty Acids in Rat

Sesamin is a specific inhibitor of Δ5 desaturation, the conversion from dihomo-γ-linolenic acid (20: 3, n-6) to arachidonic acid (AA, 20: 4, n-6). Previously, we reported that sesamin inhibited Δ5 desaturation of n-6 fatty acids in rat hepatocytes but not that of n-3 fatty acids, from 20: 4 (n-3) to eicosapentaenoic acid (EPA, 20: 5, n-3). In this study, we investigated the interaction of sesamin and EPA on Δ5 desaturation of both series and the n-6/n-3 fatty acids ratio by measuring actural fatty acid contents in vivo. Rats were fed three types of dietary oils; 1) linoleic acid (LA, 18: 2, n-6): linolenic acid (LLA, 18: 3, n-3) = 3: 1, n-6/n-3 ratio of 3: 1 (LA group), 2) LA: LLA =1: 3, n-6/n-3 ratio of 1: 3 (LLA group), 3) LA: LLA: EPA =1: 0.5: 3, n-6/n-3 ratio of 1: 3.5 (EPA group) with or without sesamin (0.5% w/w) for 4 weeks. In all groups, sesamin administration increased the content of dihomo-γ-linolenic acid (20: 3, n-6) in the liver and decreased the Δ5 desaturation index of n-6 fatty acid, the ratio of 20: 4/20: 3 (n-6). On the contrary, the Δ5 desaturation index of n-3 fatty acid, the ratio of 20: 5 + 22: 5 + 22: 6/20: 4 (n-3), was increased by the administration of sesamin. These results suggest that sesamin inhibits the A5 desaturation of n-6 fatty acid, but not that of n-3 fatty acid in rat livers. Sesamin administration decreased incorporation of EPA (n-3) and simultaneously increased the AA (n-6) content in the liver. The n-6/n-3 ratio in the liver was increased by administering sesamin under n-3 rich conditions, i.e., the LLA and EPA groups.