FISH OIL AND CHYLOMICRON METABOLISM

鱼油是一种独特的饮食脂肪，可以有效地降低空腹和 人类餐后甘油三酯水平。虽然对肝脏的抑制 甘油三酯的合成被广泛认为是导致 减少空腹甘油三酯，omega3脂肪酸的原因 (Fas)较低的乳糜粒水平几乎是未知的。这样做的目的是 项目是研究机制，并在这样做的基础上评估两个新的 方法研究乳胶粒在人体内的代谢。我们会研究这两个问题 人和大鼠确定长期补充omega3 FA是否 增强乳糜粒清除或减缓脂肪吸收/乳糜粒 分泌物。健康志愿者(n=24)将给予与临床相关的 脂肪酸乙酯的剂量(5g/d)。他们会带上橄榄油 服用4周的安慰剂，然后随机和盲目分配服用 红花油(欧米茄6多不饱和脂肪酸对照)或鱼油浓缩物 (含%EPA+DHA)，持续4周。在服用安慰剂和 主动治疗阶段我们将检验吸收假说(通过 肠道灌注量测量小肠对脂肪的吸收， 并在口服脂肪负荷后收集大便以寻找脂肪 吸收不良)，以及清除假说(通过注射自体， 用化学标记的乳胶粒测定清除动力学，以及 内源性脂蛋白和肝脂酶活性的测定)。我们 也将确定omega3脂肪酸对部分胆固醇的影响 吸收。在老鼠身上的研究将检验同样的假设，只会更多 侵犯性的。脂肪吸收将通过定量淋巴进行评估 高脂肪餐后的引流和标记的乳糜粒的积累 在血浆中使用Triton WR1339+油酸乙酯进行脂肪溶解阻断。 同源和异源乳胶粒将被注射到对照和 Omega-3 FA喂养大鼠，测定其清除率。乳糜龙会 也被注射到功能性肝切除大鼠体内，以评估如何 它们很快就会转化为残留物，并变成孤立的肝脏 测定其肝脏残留摄取率。这些研究应该 揭示了非凡的餐后饮食背后的机制 在服用omega3脂肪酸的人群中观察到低乳糜粒微粒症。他们还应该 为体内研究脂蛋白脂酶活性提供了一种新的方法。未来 研究将探索导致omega3的分子机制 黄曲霉毒素可诱导乳糜球蛋白水平降低。

Fish oils are unique dietary fats which powerfully lower both fasting and postprandial triglyceride levels in humans. Although inhibition of hepatic triglyceride synthesis is widely believed to be the reason for the reduction in fasting triglycerides, the reason why omega3 fatty acids (FAs) lower chylomicron levels is virtually unknown. The purpose of this project is to study the mechanism, and in so doing to evaluate two new methods to explore chylomicron metabolism in humans. We will study both humans and rats to determine whether chronic omega3 FA supplementation enhances chylomicron clearance or slows fat absorption/chylomicron secretion. Healthy volunteers (n=24) will be given clinically-relevant doses (5 g/d) of fatty acid ethyl esters. They will take an olive oil placebo for 4 weeks and then be randomly and blindly assigned to take either safflower oil (omega6 PUFA control) or a fish oil concentrate (containing 64% EPA+DHA) for the next 4 weeks. During the placebo and the active treatment phases we will test the absorption hypothesis (by intestinal perfusion to measure fat absorption over a length small bowel, and stool collection after an oral fat load to look for fat malabsorption), and the clearance hypothesis (by injection of autologous, chemically-labeled chylomicrons to measure clearance kinetics, and measurement of endogenous lipoprotein and hepatic lipase activities). We will also determine the effect of omega3 FAs on fractional cholesterol absorption. Studies in rats will examine the same hypotheses, only more invasively. Fat absorption will be assessed by quantitative lymphatic drainage after a high fat meal and by accumulation of labeled chylomicrons in the plasma during lipolytic blockade using Triton WR1339+ethyl oleate. Homologous and heterologous chylomicrons will be injected into control and omega3 FA fed rats and their clearance rates determined. Chylomicrons will also be injected into functionally hepatectomized rats to assess how rapidly they are converted into remnants, and into isolated livers to determine their rate of hepatic remnant uptake. These studies should reveal the mechanism behind the remarkable postprandial hypochylomicronemia observed in humans taking omega3 FAs. They should also produce a new method for studying LpL activity in vivo in humans. Future studies will explore the molecular mechanisms responsible for the omega3 FA-induced reduction in chylomicron levels.