EFFECTS OF OMEGA-3 FATTY ACIDS ON LIPID TRANSPORT

这项建议的目的是了解这些机制 当饮食中的w3脂肪酸取代w6脂肪酸时 酸可以降低血浆中的血脂。中心假设是w3脂肪 当膜中的酸取代w6脂肪酸时，可增强 脂蛋白脂酶(LPL)和肝脂酶(HL)活性。 由于增强了乳胶粒的外周递送和 极低密度脂蛋白脂肪酸和胆固醇。这些人的涌入 肝脏中的成分死亡。肝脏输入量减少 将解释死亡的极低密度脂蛋白的产生。增加了 饲喂w3脂肪酸可提高肝脂酶活性 乳杆菌和极低密度脂蛋白残留量的摄取。终于到了 假设肝脏中w3脂肪酸的富集量 膜能增强低密度脂蛋白受体的活性。极低密度脂蛋白分泌 速率、极低密度脂蛋白到低密度脂蛋白的通量和部分清除率 用饲喂0.5%胆固醇和10%鱼油的公鸡进行测量 或10%的玉米油。极低密度脂蛋白和脂肪的分泌率 从饲喂实验饲料的动物中制备肝细胞 将会被比较。LPL的合成、降解和分泌 脂肪细胞与w3或w6脂肪酸孵育后 下定决心。W3系列对HL合成的影响 降解和分泌也将在肝细胞中被确定 在文化上。脂解酶与内皮细胞的结合常数 细胞将被测量。分割率和点位 受体和受体对低密度脂蛋白和胰岛素样生长因子的降解 独立的途径将由这两种饮食决定。这个 ~(14)C蔗糖IDL和~(14)C蔗糖的分级脱除 甲基化IDL将在LPL为 被抗血清抑制，以防止IDL转化为低密度脂蛋白。 细胞膜唾液酸糖蛋白和肝素的回收 将在富含w6或w3脂肪的细胞中测定硫酸盐。 酸。最后，肝脏低密度脂蛋白受体活性将通过 ~(123)I-低密度脂蛋白、低密度脂蛋白和乳清蛋白残基与乳清蛋白结合的研究 肝膜。

The objective of the proposal is to understand the mechanisms whereby dietary w3 fatty acids when substituted for w6 fatty acids lower plasma lipids. The central hypothesis is that w3 fatty acids when substituted for w6 fatty acids in membranes enhance the activity of lipoprotein lipase (LPL) and hepatic lipase (HL). Because of the enhanced peripheral delivery of chylomicron and VLDL fatty acids and cholesterol. The influx of these constituents to the liver is deceased. The decreased hepatic input would account for the deceased VLDL production. An increased hepatic lipase activity with w3 fatty acid feeding would enhance the uptake of chylomicron and VLDL remnant. Finally it is hypothesized that enrichment of w3 fatty acids in hepatic membranes enhances LDL receptor activity. VLDL secretion rates, VLDL to LDL fluxes, and fractional removal rates will be measured in roosters fed 0.5% cholesterol and either 10% fish oil or 10% corn oil. VLDL protein and lipid secretion rates by hepatocytes prepared from animals fed the experimental diets will be compared. LPL synthesis, degradation, and secretion by adipocytes incubated with w3 or w6 fatty acids will be determined. The effect of w3 series on HL synthesis, degradation, and secretion will also be determined in hepatocytes in culture. Binding constants of lipolytic enzymes for endothelial cells will be measured. The fractional removal rate and the sites of degradation of LDL and IDL by receptor and receptor independent pathways will be determined with the two diets. The fractional removal rate of (14C) sucrose IDL and (14C) sucrose methylated IDL will be determined in animals where LPL is inhibited by antiserum to prevent conversion of IDL to LDL. Recycling of plasma membrane sialoglycoproteins and heparan sulfate will be determined in cells enriched with w6 or w3 fatty acids. Finally hepatic LDL receptor activity will be assessed by binding studies of (123I) LDL, IDL, and chylomicron remnants to liver membranes.