EFFECTS OF DIETARY FAT ON LIPID PEROXIDATIVE INJURY

膳食脂肪对脂质过氧化损伤的影响

• 批准号: 3463383
• 负责人: JEFFREY K BECKMAN
• 金额: $ 10.31万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3463383
• 关键词: atherosclerosis; cell membrane; dietary constituent; dietary lipid; dietetics; enzyme mechanism; fluorescence spectrometry; high performance liquid chromatography; laboratory rat; lipid peroxides; liver metabolism; lysosomes; microsomes; nutrition related tag; omega 3 fatty acid; pathogenic diet; phosphodiesterase inhibitors; phospholipase A2; phospholipids

We will test the hypothesis that the damaging effects associated with rat liver microsomal lipid peroxidation may be modified by replacing dietary (n-6) fatty acids with those of the (n-3) family. Two mechanisms by which such modifications may result will be explored; first, that the perioxidation of (n-3) fatty acids results in a group of specific oxidative products with less of an ability to cause injury than those derived from (n-6) fatty acid; and second, that (n-3) fatty acids inhibit phospholipase A-mediated fatty acyl release and by so doing alter the course of lipid peroxidation and the specific productis. The rational for the first mechanism is that specific toxic products of peroxidation, including notedly 4- hydroxynonenal, appear to require the (n-6) structure for their formation. The second (phospholipase) mechanism was derived from numerous studies demonstrating a strong association between lipid peroxidative events and enhanced phospholipase A activities as well as reports that dietary (n-3) fatty acids inhibit fatty acid release in platelets. Initial studeis will identify lipid peroxidative products derived from purified fatty acids using Overpressure-Layer Chromatography (OPLC) as well as HPLC and GC/MS. In parallel with these investigations we will assess the injurious effects of purified peroxidation products of (n-6) and (n- 3) fatty acid origin by measuring effects on enzyme activities and on lysosomal membrane integrity. The comparative effects of dietary (n-6) and (n-3)-fatty acids on lipid peroxidation will be assessed by feeding rats defined diets with varying proportions of corn oil ((n-6)-enriched) to menhaden oil ((n-3)-enriched) and measuring microsomal peroxidation products generated in vitro (by reduced iron) and in vivo (by CCL4). Effects of phospholipase A inhibition on microsomal lipid peroxidative products (in vitro) will be defined and compared with those formed following peroxidation of microsomes from menhaden oil-fed rats. Effects of the menhaden oil diet on microsomal phospholipase activity will also be defined. In view of the current interest in dietary (n- 3) fatty acids for the prevention of atherosclerosis, it is important to understand the effects of these compounds on lipid peroxidative injury, a potential aspect of numerous disease processes.

我们将检验一个假设， 与大鼠肝微粒体脂质过氧化反应可能被修改， 用（n-3）族脂肪酸代替膳食中的（n-6）脂肪酸。 可能导致这种修改的两种机制将是： 探索;首先，（n-3）脂肪酸的过氧化导致 在一组特定的氧化产物中， 比衍生自（n-6）脂肪酸的那些引起损伤;和第二， （n-3）脂肪酸抑制磷脂酶A介导的脂肪酰基 释放，并通过这样做改变脂质过氧化的过程， 具体的产品。 第一种机制的合理性是 过氧化反应的特定有毒产物，包括4- 羟基壬烯醛，似乎需要（n-6）结构， 阵 推导出第二种（磷脂酶）机制 大量研究表明 脂质过氧化事件和增强的磷脂酶A之间 活性以及膳食（n-3）脂肪酸抑制 血小板中的脂肪酸释放。 初始研究将确定脂质 使用纯化脂肪酸衍生的过氧化产物， 超压层色谱法（OPLC）以及HPLC， GC/MS。在这些研究的同时，我们将评估 纯化的（n-6）和（n- 3)脂肪酸来源，通过测量对酶活性的影响， 对溶酶体膜完整性的影响 的比较效果 膳食（n-6）和（n-3）-脂肪酸对脂质过氧化作用将是 通过给大鼠喂食含有不同比例的 玉米油（（n-6）-富集的）到鲱鱼油（（n-3）-富集的），以及 测量体外产生的微粒体过氧化产物 (by还原铁）和体内（通过CCL 4）。 磷脂酶的作用 对微粒体脂质过氧化产物的抑制（体外） 将被定义并与以下形成的那些进行比较 鲱鱼油喂养大鼠微粒体的过氧化作用。 影响 对微粒体磷脂酶活性的影响 也将被定义。 鉴于目前对饮食的兴趣（N- 3)脂肪酸对于预防动脉粥样硬化， 了解这些化合物对脂质的影响 过氧化损伤是许多疾病的潜在方面， 流程.