Frøyland L, Vaagenes H, Asiedu D K, Garras A, Lie O, Berge R K
Department of Clinical Biology, University of Bergen, Norway.
Lipids. 1996 Feb;31(2):169-78. doi: 10.1007/BF02522617.
Fish oils rich in n-3 fatty acids have been shown to decrease plasma lipid levels, but the underlying mechanism has not yet been elucidated. This investigation was performed in order to further clarify the effects of purified ethyl esters of eicosapentaenoic acid (EPA-EE) and docosahexaenoic acid (DHA-EE) on lipid metabolism in rats. The animals were fed EPA-EE, DHA-EE, palmitic acid, or corn oil (1 g/kg/d) by orogastric intubation along with a chow background diet for three months. At the end the animals were sacrificed. Plasma and liver lipids were measured, as well as lipid-related enzyme activities and mRNA levels. The fatty acid composition of plasma and different tissues was also determined. This study shows that, compared to the corn oil control, EPA-EE and DHA-EE lowered plasma cholesterol level, whereas only EPA-EE lowered the amount of plasma triacylglycerol. In liver peroxisomes, both EE preparations increased fatty acyl-CoA oxidase FAO activities, and neither altered 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activities. In liver microsomes, EPA-EE raised HMG-CoA reductase and acyl-CoAicholesterol acyltransferase activities, whereas DHA-EE lowered the former and did not affect the latter. Neither product altered mRNA levels for HMG-CoA reductase, low density lipoprotein-receptor, or low density lipoprotein-receptor related protein. EPA-EE lowered plasma triacylglycerol, reflecting lowered very low density lipoprotein secretion, thus the cholesterol lowering effect in EPA-EE-treated rats may be secondary to the hypotriacylglycerolemic effect. An inhibition of HMG-CoA reductase activity in DHA-EE treated rats may contribute to the hypocholesterolemic effect. The present study reports that 20:5n-3, and not 22:6n-3, is the fatty acid primarily responsible for the triacylglycerol lowering effect of fish oil. Finally, 20:5n-3 was not converted to 22:6n-3, whereas retroconversion of 22:6n-3 to 20:5n-3 was observed.
富含n-3脂肪酸的鱼油已被证明可降低血浆脂质水平，但其潜在机制尚未阐明。进行这项研究是为了进一步阐明纯化的二十碳五烯酸乙酯（EPA-EE）和二十二碳六烯酸乙酯（DHA-EE）对大鼠脂质代谢的影响。通过经口胃插管给动物喂食EPA-EE、DHA-EE、棕榈酸或玉米油（1 g/kg/d），同时给予基础饲料，持续三个月。实验结束时处死动物。测量血浆和肝脏脂质、脂质相关酶活性及mRNA水平。还测定了血浆和不同组织的脂肪酸组成。本研究表明，与玉米油对照组相比，EPA-EE和DHA-EE可降低血浆胆固醇水平，而只有EPA-EE可降低血浆三酰甘油含量。在肝脏过氧化物酶体中，两种乙酯制剂均增加了脂肪酰辅酶A氧化酶（FAO）活性，且均未改变3-羟基-3-甲基戊二酰（HMG）-辅酶A还原酶活性。在肝脏微粒体中，EPA-EE提高了HMG-辅酶A还原酶和酰基辅酶A胆固醇酰基转移酶活性，而DHA-EE降低了前者，且对后者无影响。两种产品均未改变HMG-辅酶A还原酶、低密度脂蛋白受体或低密度脂蛋白受体相关蛋白的mRNA水平。EPA-EE降低了血浆三酰甘油，反映出极低密度脂蛋白分泌减少，因此EPA-EE处理的大鼠中胆固醇降低作用可能继发于降三酰甘油作用。DHA-EE处理的大鼠中HMG-辅酶A还原酶活性的抑制可能有助于降胆固醇作用。本研究报告称，20:5n-3而非22:6n-3是鱼油降低三酰甘油作用的主要脂肪酸。最后，未观察到20:5n-3转化为22:6n-3，而观察到22:6n-3逆向转化为20:5n-3。
