The effects of fatty acids on apolipoprotein B secretion by human hepatoma cells (HEP G2)
The effects of fatty acids on apolipoprotein B secretion by human hepatoma cells (HEP G2)
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DOI：
10.1016/s0021-9150(99)00374-3
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发表时间：
2000-06-01
期刊：
影响因子：
5.3
通讯作者：
Durrington, PN
中科院分区：
文献类型：
--
作者：
Arrol, S;Mackness, MI;Durrington, PN
我们研究了脂肪酸对人肝癌细胞（Hep G2）分泌载脂蛋白B（apo B）速率的影响。当Hep G2细胞保持在组织培养瓶中时，油酸高达0.4 mM以剂量依赖性方式增加apo B分泌，而三酰甘油（TG）的增加较小，剂量依赖性不太明显。在不存在油酸的情况下，在组织培养基中积累的载脂蛋白B主要是密度高于极低密度脂蛋白（VLDL）的脂蛋白。然而，当用油酸刺激分泌速率时，含载脂蛋白B的脂蛋白的密度变得较低。我们推测Hep G2细胞对新分泌的VLDL有较高的脂解率，这可以解释油酸对TG的影响相对于载脂蛋白B在培养基中的积累相对较小，以及载脂蛋白B在比VLDL密度更高的脂蛋白中的优势，当油酸刺激VLDL分泌率时，这种优势变得不那么明显。为了验证这一假设，将培养的Hep G2细胞转移到含有Cytodex珠的柱中，允许其连续灌注培养基，使得新分泌的VLDL不与细胞保持接触。从灌流液中回收的载脂蛋白B主要是VLDL范围内的脂蛋白，在灌流液中测量的TG表明富含TG的脂蛋白的真实分泌速率显著高于在与细胞接触的培养基中积累的TG所反映的分泌速率。因此，在Hep G2细胞的培养基中测量的Apo B可能更好地反映VLDL分泌，即使由于通过脂解去除TG而将其包含在更高密度的脂蛋白中。接下来研究饱和脂肪酸（SFA）、单不饱和脂肪酸（MUFA）和多不饱和脂肪酸（PUFA）对维持在组织培养瓶中的Hep G2细胞的apo B（apo B）分泌的影响。除硬脂酸（C18：0）外，SFA（0.4 mM）均增加apo B分泌。月桂酸（C12：0）使apo B分泌增加32%，肉豆蔻酸（C14：0）使apo B分泌增加41%（P
We have investigated the effect of fatty acids on the rate of apolipoprotein B (apo B) secretion by human hepatoma cells (Hep G2). When Hep G2 cells were maintained in tissue culture flasks oleic acid up to 0.4 mM increased apo B secretion in a dose-dependent manner, whereas increases in triacylglycerol (TG) were smaller and dose dependency was less evident. In the absence of oleic acid, apo B accumulating in the tissue culture medium was predominantly in lipoproteins of higher density than very low density lipoproteins (VLDL). However, when the rate of secretion was stimulated with oleic acid the apo B-containing lipoproteins became lower in density. We postulated that there was a high rate of lipolysis of newly secreted VLDL by Hep G2 cells, which would account both for the relatively smaller effect of oleic acid on TG as opposed to apo B accumulating in the culture medium and the predominance of apo B in lipoproteins of a higher density than VLDL, which became less evident when VLDL secretory rates were stimulated by oleic acid. To test this hypothesis, cultured Hep G2 cells were transferred to columns containing Cytodex beads, permitting their continuous perfusion with culture medium so that newly secreted VLDL did not remain in contact with the cells. Apo B recovered from the perfusate was largely in VLDL range lipoproteins and the TG measured in the perfusate indicated that the true secretory rate of TG-rich lipoproteins was substantially higher than had been reflected by TG accumulating in culture medium left in contact with cells. Apo B measured in the culture medium of Hep G2 cells may thus be a better reflection of VLDL secretion, even though it is contained in higher density lipoproteins due to removal of TG by lipolysis. The effects of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) on apo B (apo B) secretion by Hep G2 cells maintained in tissue culture flasks were next investigated. SFA (0.4 mM), with the exception of stearic acid (C18:0), increased apo B secretion. Lauric acid (C12:0) increased apo B secretion by 32%, myristic acid (C14:0) by 41% (P