MECHANISM OF ATHEROGENIC LIPID RESPONSE TO W-3 FISH OILS

Omega-3脂肪酸(n-3FA)可能在原发性和继发性中都有作用 预防冠心病(CAD)。它们的保护作用是 部分归因于它们的降脂性能。N-3FA一致 降低血浆甘油三酯(TG)。然而，它们对低密度脂蛋白(LDL)的影响 和高密度脂蛋白(高密度脂蛋白)是可变的。我们观察到在 一些II型糖尿病(DM)患者n-3FA没有改善 血浆低密度脂蛋白或高密度脂蛋白，甚至升高血浆蛋白(Apo)B，表明 低密度脂蛋白颗粒数量的增加。我们在Zucker大鼠身上所做的工作 胰岛素抵抗肥胖症和高甘油三酯血症模型，提示n- 3FA通过抑制肝脏脂酶活性降低甘油三酯。 我们的工作使我们假设n-3FA抑制肝脏脂肪生成 酵素。这导致非常低密度的Tg降低 脂蛋白(VLDL)及其相关的颗粒尺寸减小； 这与脂蛋白脂酶(LPL)的同时增加有关 活动，加速极低密度脂蛋白向低密度脂蛋白的转化。然而，任何由此产生的 血浆低密度脂蛋白升高更有可能发生在患有异常的受试者 治疗前血脂谱或载脂蛋白E表型异常。N-3FA也 取代极低密度脂蛋白中的脂肪酸(FA)，改变脂解特性。类型 糖尿病患者更容易受到n-3FA的影响，因为他们有 极低密度脂蛋白产量增加，低密度脂蛋白储备有所减少。 我们计划在四组II型糖尿病患者中挑战这些假设， 根据他们的血浆脂类(正常，IIa，IIb， IV/V高脂血症)。我们将测量Tg含量，Fa组成和 极低密度脂蛋白颗粒大小、脂蛋白脂酶活性及体内外比率 维拉帕米治疗12周前后极低密度脂蛋白脂解为低密度脂蛋白 N-3FA。观察到的反应将与患者之前的 治疗：血脂谱、脂谱和载脂蛋白E表型。这个 糖尿病患者的结果将与年龄的结果进行比较， 性别和体重与非糖尿病对照组相匹配。 II型糖尿病与冠心病增加两到三倍相关。这个 我们在一些受试者中观察到的不良脂质反应并不局限于此。 N-3FA治疗，但可发生在对纤维酸衍生物的反应中， 胰岛素或减肥。我们的研究应该提供信息，可以 提高2型糖尿病的临床管理水平。

Omega-3 fatty acids (n-3FA) may have a role both in primary and secondary prevention of coronary artery disease (CAD). Their protective effects are partially attributed their lipid lowering properties. n-3FA consistently lower the plasma triglycerides (TG). However their effects on low (LDL) and high density (HDL) lipoproteins are variable. We observed that in some patients with type II diabetes mellitus (DM), n-3FA fail to improve plasma LDL or HDL and even raise the plasma protein (apo) B, suggesting an increase in the number of LDL particles. Our work in Zucker rats, an insulin resistant obese and hypertriglyceridemic model, suggested that n- 3FA lower the TG by suppressing the hepatic lipogenic enzymes. Our work lead us to postulate that of n-3FA suppress hepatic lipogenic enzymes. This causes a reduction in the TG in very low density lipoproteins (VLDL) and an associated decrease in their particle size; which , together with a concurrent increase in lipoprotein lipase (LPL) activity, expedites the conversion of VlDL to LDL. However, any resultant increase in plasma LDL is more likely to occur in subjects with an abnormal pre-treatment lipid profile or an abnormal apoE phenotype. n-3FA also replace the fatty acids (FA) in VLDL an d alter lipolytic properties. Type II diabetics are more susceptible to the effects of n-3FA, since they have increased VLDL production and some decrease in their LPL reserve. We plan to challenge these hypothesis in four groups of type II diabetics, categorized on the basis of their plasma lipids (normal, types IIa, IIb, IV/V hyperlipidemias). We shall measure the TG content, Fa composition and particle size of VLDL, LPL activity and the rate of in vivo and in vitro lipolysis of VLDL into LDL before, during and after 12 wks treatment with n-3FA. The responses observed will be correlated with patients' pre- treatment lipid profiles and lipid profiles and apoE phenotypes. The results obtained in diabetics will be compared to those obtained in age, sex and weight matched non-diabetic controls. Type II DM associated with a two to three-fold increase in CAD. The unfavorable lipid response we have observed in some subjects is not limited to n-3FA therapy but can occur in response to fibric acid derivatives, insulin or weight loss. Our study should provide information which can improve the clinical management of type II DM.