FISH OIL AND CHYLOMICRON METABOLISM

鱼油是一种独特的膳食脂肪，它能有效降低空腹血糖， 人的餐后甘油三酯水平。虽然抑制肝脏 甘油三酸酯合成被广泛认为是 空腹甘油三酯的减少，欧米茄3脂肪酸的原因 (FAs)较低的乳糜微粒水平实际上是未知的。这样做的目的 项目是研究机制，并在这样做，以评估两个新的 方法探索乳糜微粒代谢在人类。我们将研究两者 以确定长期补充ω 3 FA 增强乳糜微粒清除或减缓脂肪吸收/乳糜微粒 分泌物健康志愿者（n=24）将接受临床相关的 剂量（5 g/d）的脂肪酸乙酯。他们会用橄榄油 安慰剂4周，然后随机盲法分配服用 红花油（ω 6 PUFA对照）或鱼油浓缩物 （含有64%的EPA+DHA）。在安慰剂和 积极治疗阶段，我们将测试吸收假设（通过 肠灌注以测量小肠长度上的脂肪吸收， 并在口服脂肪负荷后收集粪便以寻找脂肪 吸收不良）和清除假说（通过注射自体， 化学标记的乳糜微粒，以测量清除动力学，和 内源性脂蛋白和肝脂酶活性的测量）。我们 还将确定ω 3脂肪酸对胆固醇分数的影响 吸收对大鼠的研究将检验同样的假设，只是更多 侵入性地脂肪吸收将通过定量淋巴细胞计数评估。 高脂餐后引流和标记乳糜微粒的积聚 在使用Triton WR 1339+油酸乙酯的脂解阻断期间的血浆中。 将同种和异种乳糜微粒注射到对照组中， ω 3FA喂养的大鼠，并测定它们的清除率。乳糜微粒会 也被注射到功能性肝切除大鼠，以评估如何 它们迅速转化为残余物，并转化为孤立的肝脏， 确定其肝残留物摄取率。这些研究应 揭示了餐后饮食中 在服用ω 3 FA的人中观察到低乳糜微粒血症。他们也应该 产生一种研究人体内LpL活性的新方法。未来 研究将探索负责omega 3的分子机制 FA诱导乳糜微粒水平降低。

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.