基于白色脂肪棕色化的n-3多不饱和脂肪酸减重机制研究

旨在探讨n-3 PUFA的减重效应及其促进白色脂肪组织棕色化的分子机制,以期为预防和治疗肥胖症提供新思路,为减肥食谱中n-3 PUFAs的应用提供参考.20只6周龄SPF级C57BL/6雄性小鼠适应性喂养1w,按体重随机分为正常组、高脂猪油组(SFAs组)、高脂大豆油组(n-6 PUFAs组)和高脂亚麻籽油组(n-3 ...     

二十二碳六烯酸与胎儿、婴幼儿

二十二碳六烯酸（docosahexaenoicacids．DHA）是n-3系列一种长链多不饱和脂肪酸（PUFAs），俗称“脑黄金”。多不饱和脂肪酸是人类的必需脂肪酸，在体内不能合成，必须由食物供给．对人体健康起着十分重要的作用。自从20世纪80年代中期Bang和Dyerberg提出爱斯基摩人较低的心血管病死亡率可能与他们食用含高浓度的n-3PUFAs的海生食物有关．掀起了研究DHA和EPA的热潮。     

不同膳食脂肪酸构成对乳腺癌大鼠BRCA1表达的影响

目的探讨不同比例n-6/n-3多不饱和脂肪酸(PUFA)对甲基亚硝基脲(MNU)诱导的乳腺癌大鼠乳腺癌易感基因(BRCA1)表达的影响。方法雌性SD大鼠65只随机分为5组,即n-6PUFA组、10:1n-6/n-3组、5:1n-6/n-3组、1:1n-6/n-3组和正常对照组,前四组以50mg/kg体重MNU单次腹腔注射诱导大鼠乳腺肿瘤发生,正常对照组注射等体积无菌生理盐水。给药后立即分组喂养不同饲料,并在8周和18周时处死动物剪取乳腺组织,利用RT-PCR和Westernblot技术检测组织中BRCA1mRNA和蛋白表达状况。结果四组乳腺癌大鼠BRCA1表达较正常对照组均有所下降,四组中BRCA1的表达以1:1n-6/n-3组最强,并随n-6/n-3比值增大而下降。结论不同膳食脂肪酸构成对MNU诱导的乳腺癌大鼠BRCA1的表达具有不同影响,1:1n-6/n-3膳食脂肪酸构成能有效抑制乳腺癌大鼠BRCA1表达的下降。     

n-3多不饱和脂肪酸对白色脂肪棕色化影响的中枢及外周机制

肥胖是当下全球性的健康问题,是多种慢性病的潜在危险因素。现代人群对于肥胖的关注度越来越高,因为全球肥胖率在逐步上升中。在体内有两种脂肪组织：白色脂肪与棕色脂肪。白色脂肪组织储存能量,而棕色脂肪组织消耗能量。研究发现,n-3多不饱和脂肪酸饮食减肥效果明显,其机制可能与其促进白色脂肪棕色化有关。与单独的饱和脂肪酸饮食相比,n-3 PUFAs饮食可在脂肪细胞层面上抑制肥胖的产生和发展。在中枢机制中,n-3 PUFAs通过对下丘脑的调控,影响TRP家族、AMPK、瘦素和肾上腺素的表达,促进脂肪细胞线粒体的生成,促进白色脂肪棕色化,具有产热功能,消耗能量。在外周机制中,n-3 PUFAs通过影响3T3-L1脂肪细胞、脂肪细胞的转录、白色脂肪组织中棕色化标志基因表达,促进白色脂肪细胞棕色化。文章就n-3多不饱和脂肪酸对中枢及外周脂肪细胞的影响促进白色脂肪棕色化的机制作一综述。提示人们可以通过调整饮食模式,改变摄入的脂肪类型,多摄入n-3多不饱和脂肪酸,促进白色脂肪组织的消耗,有助于达到减脂的目的。     

n-3多不饱和脂肪酸在不同疾病中的研究进展

<正>n-3多不饱和脂肪酸(n-3PUFAs)指多不饱和脂肪酸中第1个不饱和键出现在碳链甲基端的第3位,对人体健康状况起着重要的作用,n-3PUFAs主要包括α-亚麻酸(α-linolenic aicd,ALA,18:3n-3),二十碳五烯酸(eicosapentaenoic acid,EPA,20:5n-3),二十二碳六烯酸(docosahexaenoic acid,DHA,22:6n-3)等,其中含丰富的α-亚麻酸是人体     

n-3多不饱和脂肪酸类药物在心血管疾病中的临床应用进展

许多临床试验表明n-3多不饱和脂肪酸(n-3 PUFAs)对于冠心病、血脂异常和心力衰竭等人群均具有保护作用,而且已有建议推荐心肌梗死后患者和高甘油三酯血症人群口服此类提纯药物。但在应用过程中,仍有一些值得临床关注的问题,如药物安全性、药物成分和用量等。笔者认为,随着对n-3 PUFAs药物的深入研究,其将有更广阔的应用前景。     

n-3系多烯酸摄取量的探讨

n-3系多烯酸具有防治心血管疾病、促进脑组织及视网膜的正常生长发育等生理作用,因此越来越引起人们摄取的兴趣。从目前的膳食结构来看,摄取n-3系多烯酸是十分必要的。如何正确的摄取,以充分发挥n-3系多烯酸对人体的健康作用及避免不良反应是人们摄取及开发这方面的保健食品和药物时值得注意的问题。     

n-3系多烯酸摄取量的探讨

n-3系多烯酸具有防治心血管疾病、促进脑组织及视网膜的正常生长发育等生理作用，因此越来越引起人们摄取的兴趣。从目前的膳食结构来看，摄取n-3系多烯酸是十分必要的。如何正确的摄取，以充分发挥n-3系多烯酸对人体的健康作用及避免不良反应是人们摄取及开发这方面的保健食品和药物时值得注意的问题。     

n-3系多烯酸摄取量的探讨

n-3系多烯酸具有防治心血管疾病、促进脑组织及视网膜的正常生长发育等生理作用,因此越来越引起人们摄取的兴趣.从目前的膳食结构来看,摄取n-3系多烯酸是十分必要的.如何正确的摄取,以充分发挥n-3系多烯酸对人体的健康作用及避免不良反应是人们摄取及开发这方面的保健食品和药物时值得注意的问题.     

前列腺素类、巯基和一氧化氮对黄芪皂苷Ⅳ胃保护作用的影响

前期研究发现,富含n-3多不饱和脂肪酸(n-3PUFA)的饮食能缓解由脂多糖(LPS)诱导的系统性炎症小鼠食欲及探究行为的减退,但含n-3PUFA的饮食对不同炎症条件下行为的作用鲜有报道。为此作者进行了以下实验。实验选用雄性ddY小鼠,实验饲料中有富含n-3PUFA的紫苏子油(质量分数10%,n-3     

Fish oil fatty acids as cardiovascular drugs

Starting in the 1970s the hypothesis that the low mortality from coronary heart disease among the Greenland Eskimos was due to their high consumption of n-3 fish oil fatty acids, initiated many studies to find if the n-3 polyunsaturated fatty acids in fish oils (PUFAs) could prevent cardiac atherosclerosis. To date this possibility has not achieved clinical recognition. The recent literature shows an increase of intervention studies to learn if the fish oil fatty acids can reduce mortality from sudden cardiac death, and the mechanism(s) of such a protective effect. Indeed the most definite beneficial cardiac action of these n-3 PUFAs seems now to be their ability in the short term to prevent sudden cardiac death. It is apparent that over long periods of time the n-3 fish oil fatty acids also prevent atherosclerosis. Definition of the fatty acids to which I will be referring in the text: n-6 (omega-6) polyunsaturated fatty acids; linoleic acid (18:2n-6, LA); arachidonic acid (C20:4n-6, AA). n-3 (omega-3) fatty acids; alpha-linolenic acid (18:3n-3, ALA); eicosapentaenoic acid (20:5n-3, EPA); docosahexaenoic acid (C22:6n-3, DHA). The bold, underlined abbreviation will appear in the text to identify the fatty acid being discussed.     

Chronic dietary changes in n-6/n-3 polyunsaturated fatty acid ratios cause developmental delay and reduce social interest in mice

Polyunsaturated fatty acids (PUFAs) are one of the main cellular building blocks, and dietary changes in PUFA composition are proposed as a potential route to influence brain development. For example, initial studies indicated that there is a relation between blood omega-6(n-6)/omega-3(n-3) PUFA ratios and neurodevelopmental disease diagnosis. To study the consequences of dietary n-6/n-3 PUFA ratio changes, we investigated the impact of a n-3 supplemented and n-3 deficient diet in developing BTBR T?+?Itpr3tf/J (BTBR) – a mouse inbred strain displaying Autism Spectrum Disorder (ASD)-like symptomatology - and control C57BL/6J mice. This study showed that pre- and postnatal changed dietary n-6/n-3 ratio intake has a major impact on blood and brain PUFA composition, and led to delayed physical development and puberty onset in both strains. The PUFA induced developmental delay did not impact adult cognitive performance, but resulted in reduced social interest, a main ASD behavioral feature. Thus, both chronic dietary n-3 PUFA supplementation and depletion may not be beneficial.     

Effects of polyunsaturated fatty acids on calcium response and degranulation from RBL-2H3 cells

To investigate the biological activity of various polyunsaturated fatty acids (PUFAs) on the allergic reaction, we examined the effects of six PUFAs and two saturated fatty acids on calcium response and degranulation from rat basophilic leukemia (RBL-2H3) cells. Between 20 and 40 microM of six PUFAs (omega-6 series: arachidonic acid [AA, C20:4], gamma-linolenic acid [gamma-LN, C18:3] and linoleic acid [LA, C18:2]; omega-3 series: alpha-linolenic acids [alpha-LN, C18:3] and eicosapentaenoic acid [EPA, C20:5]; and omega-9 series: oleic acid [OLE, C18:1]), or two saturated fatty acids (stearic acid [STA, C18:0] and arachidic acid [AD, C20:0]) were used to examine the effects on calcium response and degranulation from RBL-2H3 cells. Calcium response was monitored using the fluorescent calcium indicator fura-2, while degranulation was monitored by measuring histamine release from the cells. Three omega-6 PUFAs (AA, alpha-LN and LA) dose-dependently increased the cytosolic free-calcium concentration and histamine release from RBL-2H3 cells. This phenomenon was specific to the omega-6 PUFAs, the omega-3 PUFAs (alpha-LA and EPA), omega-9 PUFA (OLE) and the saturated fatty acids (STA and AD) had no effect. The increase in the cytosolic free-calcium concentration caused by the omega-6 PUFAs depended on the existence of external calcium, cell viability and the cellular IP(3) levels remained unchanged throughout the experiment. These results suggest that omega-6 PUFAs work as direct mediators of calcium signaling pathways in RBL-2H3 cells.     

海狗油ω-3多不饱和脂肪酸对大鼠脂肪肝的治疗作用

目的观察海狗油ω 3多不饱和脂肪酸 (海狗油 )对大鼠脂肪肝的治疗作用。方法小剂量四氯化碳合并高脂饲料复制大鼠脂肪肝模型 7周后 ,模型组ig等体积橄榄油 ,阳性药组ig辛伐他汀 4mg/kg ,海狗油低、中、高剂量组分别ig海狗油 0 .5、1.6、4 .8g/kg ,1次 /d ,连续 8周 ,正常大鼠作为空白组。以肝脏的重量、肝脂质含量、6 酮 前列腺素F1α与血栓素B2 比值 (6 keto PGF1α/TXB2 )、脂质过氧化作用和病理检查为主要衡量指标 ,观察其防治效果。结果海狗油各组与模型组相比大鼠肝重减轻 ,肝组织中甘油三脂、总胆固醇、丙二醛、游离脂肪酸含量显著降低 ,超氧化物歧化酶活性升高 ,6 keto PGF1α/TXB2 增加 ,病理检查苏丹Ⅲ染色、HE染色和细胞色素P4 5 0 2E1免疫组织化学染色显示肝内脂变减轻 ,表达减弱。结论海狗油对实验性脂肪肝的形成具有治疗作用。     

ω-3多不饱和脂肪酸治疗非酒精性脂肪性肝病的研究进展

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是由多种危险因素,如营养过剩、胰岛素抵抗(insulin resistance,IR)及相关代谢紊乱等诱导的慢性肝损伤,是代谢综合征在肝脏的病理表现。其病程的进展表现为非酒精性单纯性脂肪肝(nonalcoholic simple fatty liver,NAFL)、非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)、脂肪性肝纤维化和脂肪性肝硬化。NAFLD患病率逐年升高,已成为我国最常见的慢性肝病之一。NAFLD的治疗主要为增加运动、健康饮食等基础治疗,药物治疗尚未达成共识。ω-3多不饱和脂肪酸(ω-3 polyunsattrated fatty acids,ω-3PUFAs)具有调节血脂的功能。NAFLD患者ω-3PUFAs水平较低,增加饮食中的ω-3PUFAs可以延缓病情进展,改善肝脏脂代谢的失衡和肝细胞的炎性损伤。本文主要就ω-3PUFAs对NAFLD治疗的研究进展作一综述。     

Effects of long chain ω-3 fatty acids on metalloproteinases and their inhibitors in combined dyslipidemia patients

We evaluate the effect of a standardized dietary supplementation with ω-3 polyunsaturated fatty acids (n-3 PUFAs) on the level of some markers of vascular remodeling in patients with combined dyslipidemia. Three hundred and thirty-three patients received placebo or n-3 PUFAs for 6 months. We evaluated body mass index, glycemic profile, blood pressure, lipid profile, lipoprotein(a), plasminogen activator inhibitor-1, homocysteine, fibrinogen, high-sensitivity C reactive protein, ADP, MMP-2 and MMP-9, and tissue inhibitors of metalloproteinase-1 and -2. A significant increase of high-density lipoprotein-cholesterol, and a significant decrease of triglycerides were present after 3 and 6 months with n-3 PUFAs intake. A significant plasminogen activator inhibitor-1, fibrinogen and high-sensitivity C reactive protein decrease was obtained after 3 and 6 months and a significant ADP increase was observed after 3 and 6 months of n-3 PUFAs. A significant MMP-2, MMP-9, tissue inhibitors of metalloproteinase-1 and tissue inhibitors of metalloproteinase-2 decrease was obtained after 6 months compared to the baseline value with n-3 PUFAs intake. n-3 PUFAs give a better lipid profile and a better improvement of coagulation, fibrinolytic and inflammatory parameters than placebo. Furthermore, lowers levels of MMP-2, MMP-9 and their tissue inhibitors are obtained with n-3 PUFAs compared to placebo.     

Dietary n-3 PUFAs Deficiency Increases Vulnerability to Inflammation-Induced Spatial Memory Impairment

Dietary n-3 polyunsaturated fatty acids (PUFAs) are critical components of inflammatory response and memory impairment. However, the mechanisms underlying the sensitizing effects of low n-3 PUFAs in the brain for the development of memory impairment following inflammation are still poorly understood. In this study, we examined how a 2-month n-3 PUFAs deficiency from pre-puberty to adulthood could increase vulnerability to the effect of inflammatory event on spatial memory in mice. Mice were given diets balanced or deficient in n-3 PUFAs for a 2-month period starting at post-natal day 21, followed by a peripheral administration of lipopolysaccharide (LPS), a bacterial endotoxin, at adulthood. We first showed that spatial memory performance was altered after LPS challenge only in n-3 PUFA-deficient mice that displayed lower n-3/n-6 PUFA ratio in the hippocampus. Importantly, long-term depression (LTD), but not long-term potentiation (LTP) was impaired in the hippocampus of LPS-treated n-3 PUFA-deficient mice. Proinflammatory cytokine levels were increased in the plasma of both n-3 PUFA-deficient and n-3 PUFA-balanced mice. However, only n-3 PUFA-balanced mice showed an increase in cytokine expression in the hippocampus in response to LPS. In addition, n-3 PUFA-deficient mice displayed higher glucocorticoid levels in response to LPS as compared with n-3 PUFA-balanced mice. These results indicate a role for n-3 PUFA imbalance in the sensitization of the hippocampal synaptic plasticity to inflammatory stimuli, which is likely to contribute to spatial memory impairment.     

The factor in EDHF: Cytochrome P450 derived lipid mediators and vascular signaling

Cytochrome P450 (CYP) epoxygenases metabolize arachidonic acid to generate epoxyeicosatrienoic acids (EETs). The latter are biologically active and reported to act as an endothelium-derived hyperpolarizing factor (EDHF) as well as to affect angiogenic and inflammatory signaling pathways. In addition to arachidonic acid, the CYP epoxygenases also metabolize the Ω-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid and docosahexaenoic acid, to generate bioactive lipid epoxide mediators. The latter can be more potent than the EETs but their actions are under investigated. The Ω3-epoxides, like the EETs, are metabolized by the soluble epoxide hydrolase to corresponding diols and epoxide hydrolase inhibition increases epoxide levels and demonstrates anti-hypertensive as well as anti-inflammatory effects. It seems that the overall consequences of CYP epoxygenase activation largely depend on enzyme substrate preference and the endogenous Ω-3/Ω-6 PUFA ratio. This review outlines the evidence for a physiological role for EETs in the regulation of vascular homeostasis.     

Investigation of long chain omega‐3 PUFAs on arterial blood pressure,vascular reactivity and survival in angiotensin II‐infused Apolipoprotein E‐knockout mice

Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease. Long chain omega‐3 polyunsaturated fatty acids (LC n‐3 PUFAs) decrease inflammation and oxidative stress in an angiotensin II‐infused apolipoprotein E‐knockout (ApoE^?/?) mouse model of AAA. This study investigated the effects of LC n‐3 PUFAs on blood pressure and vascular reactivity in fourteen angiotensin II‐infused ApoE^?/? male mice. Blood pressure was obtained using a non‐invasive tail cuff method and whole blood was collected by cardiac puncture. Vascular reactivity of the thoracic aorta was assessed using wire myography and activation of endothelial nitric oxide synthase (eNOS) was determined by immunohistochemistry. A high LC n‐3 PUFA diet increased the omega‐3 index and reduced the n‐6 to n‐3 PUFA ratio. At day 10 post‐infusion with angiotensin II, there was no difference in systolic blood pressure or diastolic blood pressure in mice fed the high or low n‐3 PUFA diets. The high LC n‐3 PUFA diet resulted in a non‐significant trend for delay in time to death from abdominal aortic rupture. Vascular reactivity and eNOS activation remained unchanged in mice fed the high compared to the low LC n‐3 PUFA diet. This study argues against direct improvement in vascular reactivity in ApoE^?/? mice that were supplemented with n‐3 PUFA for 8 weeks prior to infusion with angiotensin II.     

mCPP-induced hypophagia in rats is unaffected by the profile of dietary unsaturated fatty acids

The n-3 and n-6 polyunsaturated fatty acids (PUFAs) have been shown to modify central serotonergic parameters relevant to ingestive behavior. Evidence suggests an association between the 5-HT(2C) receptor and fat intake. The present research sought to examine the role of the 5-HT(2C) receptor subtype on food intake when diets with different fatty acid compositions are consumed. The effects of 1-(3-chlorophenyl)piperazine (mCPP) on consumption of both low-fat (Experiment 1) and high-fat diets (Experiment 2) differing in their predominant PUFA profiles were compared in rats. Regardless of the PUFA profile, mCPP induced hypophagia within each experiment. Although the present results lend further support to a large body of evidence demonstrating the ability of mCPP to reduce food intake, they do not support the idea that the essential fatty acid composition of the diet can differentially modulate mCPP-induced hypophagia.