Murthy S, Born E, Mathur S, Field F J
Department of Internal Medicine, College of Medicine, University of Iowa, Iowa City 52242, USA.
J Lipid Res. 1998 Jun;39(6):1254-62.
Oxidized lipids present in atherogenic lipoproteins are derived, in part, from the diet. To address the effects of an oxidized lipid on intestinal lipoprotein assembly and secretion, CaCo-2 cells were incubated with 13-HODE or its native fatty acid, linoleic acid, and triacylglycerol-rich lipoprotein synthesis and secretion were investigated. 13-HODE was readily taken up by cells and esterified to lipids. Although both fatty acids were largely esterified to neutral lipids, in comparison to neutral lipids containing linoleic acid, a greater proportion of cellular neutral lipids containing 13-HODE and/or its metabolites was secreted. Compared to linoleic acid, however, 13-HODE caused less triacylglycerol, derived from de novo synthesis, and less triacylglycerol mass to be secreted. Cells incubated with both linoleic acid and 13-HODE together secreted less triacylglycerol mass than did cells incubated with linoleic acid alone. Less newly synthesized apoB and apoB mass were secreted by cells incubated with 13-HODE without altering the abundance of apoB mRNA. The fraction of newly synthesized apoB translocated into the secretory pathway of cells exposed to 13-HODE was significantly less than that observed in cells incubated with linolenic acid, suggesting that 13-HODE interfered with the assembly and secretion of triacylglycerol-rich lipoprotein particles.
致动脉粥样硬化脂蛋白中存在的氧化脂质部分来源于饮食。为了研究氧化脂质对肠道脂蛋白组装和分泌的影响,将CaCo-2细胞与13-羟基十八碳二烯酸(13-HODE)或其天然脂肪酸亚油酸以及富含三酰甘油的脂蛋白合成和分泌进行了研究。13-HODE很容易被细胞摄取并酯化为脂质。尽管两种脂肪酸都大量酯化为中性脂质,但与含有亚油酸的中性脂质相比,含有13-HODE和/或其代谢物的细胞中性脂质分泌比例更高。然而,与亚油酸相比,13-HODE导致从头合成产生的三酰甘油减少,分泌的三酰甘油质量也减少。同时用亚油酸和13-HODE处理的细胞分泌的三酰甘油质量比单独用亚油酸处理的细胞少。用13-HODE处理的细胞分泌的新合成载脂蛋白B(apoB)和apoB质量减少,而不改变apoB mRNA的丰度。暴露于13-HODE的细胞中新合成的apoB转运到分泌途径中的比例明显低于用亚麻酸处理的细胞,这表明13-HODE干扰了富含三酰甘油的脂蛋白颗粒的组装和分泌。