MECHANISM OF ATHEROGENIC LIPID RESPONSE TO W-3 FISH OILS

ω-3脂肪酸（n-3FA）可能在原发性和继发性 预防冠状动脉疾病（CAD）。 它们的保护作用是 部分归因于它们的降脂特性。 n-3FA一致 降低血浆甘油三酯（TG）。 对低密度脂蛋白（LDL）的影响 和高密度脂蛋白（HDL）是可变的。 我们观察到， 部分II型糖尿病（DM）患者，n-3FA未能改善 血浆低密度脂蛋白或高密度脂蛋白，甚至提高血浆蛋白（载脂蛋白）B，表明 LDL颗粒数量增加。 我们在Zucker大鼠中的工作， 胰岛素抵抗性肥胖和高脂血症模型，提示n- 3FA通过抑制肝脏脂肪生成酶降低TG。 我们的工作使我们推测n-3FA抑制肝脏脂肪生成 内切酶 这导致在非常低的密度下TG降低 脂蛋白（VLDL）及其颗粒大小的相关降低; 与脂蛋白脂酶（LPL）的同时增加， 活性，加速VLDL转化为LDL。 然而，任何结果 血浆LDL升高更可能发生在具有异常LDL水平的受试者中。 治疗前血脂谱或异常apoE表型。N-3FA还 取代VLDL中的脂肪酸（FA）并改变脂解性质。 类型 II型糖尿病患者更容易受到n-3FA的影响，因为他们 VLDL的产生增加，LPL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， 根据其血浆脂质（正常，IIa，IIb， IV/V高血压）。 我们将测量TG含量、Fa组成和 VLDL颗粒大小、LPL活性及体内外结合率 VLDL在12周治疗前、治疗期间和治疗后脂肪分解为LDL， n-3FA。 观察到的反应将与患者的预- 治疗血脂谱和血脂谱和apoE表型。 的 将在糖尿病患者中获得的结果与在老年人中获得的结果进行比较， 性别和体重匹配的非糖尿病对照。 II型糖尿病与CAD增加2至3倍相关。的 我们在一些受试者中观察到的不利的脂质反应并不限于 但也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， 改善II型糖尿病的临床管理。

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.