Regulation of triglyceride-rich lipoprotein secretion by fatty acids in CaCo-2 cells.
Regulation of triglyceride-rich lipoprotein secretion by fatty acids in CaCo-2 cells.
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发表时间：
1988-11
影响因子：
6.5
通讯作者：
F. Field;E. Albright;S. Mathur
中科院分区：
文献类型：
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作者：
F. Field;E. Albright;S. Mathur
研究了脂肪酸对CaCo-2细胞分泌富甘油三酯脂蛋白（d < 1.006 g/ml）的影响。在所研究的脂肪酸中，油酸（18:1）是富甘油三酯脂蛋白中新合成甘油三酯分泌的最有效刺激物，其次是18:2、18:3和16:0 = 14:0。所有脂肪酸都增加了细胞内甘油三酯的合成。脂肪酸14:0,16:0,18:2和18.3引起类似的增加；然而，18:1导致甘油三酯合成率最高。采用油酸（18:1）进一步研究CaCo-2细胞分泌密度小于1.006 g/ml的脂蛋白。随着油酸浓度的增加，细胞内甘油三酯的合成也逐步增加。然而，在250微米以上的脂肪酸中，富甘油三酯脂蛋白中新合成的甘油三酯分泌趋于平稳，表明分泌途径饱和。油酸刺激甘油三酯合成后，富甘油三酯脂蛋白中分泌的放射性标记甘油三酯最初被延迟，导致分泌呈s形曲线。这在没有与脂肪酸孵育的对照细胞中最为明显。与对照细胞相比，油酸培养的细胞在富含甘油三酯的脂蛋白中分泌了更多新合成的甘油三酯。密度小于1.006 g/ml的脂蛋白的分泌依赖于蛋白质合成和正常的微管功能，环己亚胺和秋水仙碱显著降低甘油三酯运输而不改变细胞甘油三酯合成。与对照细胞相比，油酸培养液中密度小于1.006 g/ml的脂蛋白中甘油三酯和未酯化胆固醇的质量分别增加了57%和244%。24小时，0.17%的密度小于1.006 g/ml的脂蛋白被吸收和降解。在同一时期，大约50%的脂蛋白甘油三酯被水解。在油酸刺激脂蛋白分泌四倍的条件下，HMG-CoA还原酶和ACAT的活性与对照细胞的活性没有变化。这些数据表明CaCo-2细胞分泌密度小于1.006 g/ml的富含甘油三酯的脂蛋白来响应培养基中的脂肪酸。富含甘油三酯的脂蛋白分泌是一个饱和的过程，依赖于蛋白质合成和正常的微管功能。在密度小于1.006 g/ml的脂蛋白中，富含甘油三酯的脂蛋白分泌增加，同时甘油三酯质量增加。24小时，显著后泌
The effect of fatty acids on secretion of triglyceride-rich lipoprotein (d less than 1.006 g/ml) by CaCo-2 cells was studied. Of the fatty acids studied, oleic acid (18:1) was the most potent stimulator of newly synthesized triglyceride secretion in triglyceride-rich lipoproteins followed in descending order by 18:2, 18:3, and 16:0 = 14:0. All the fatty acids increased intracellular triglyceride synthesis. Fatty acids 14:0, 16:0, 18:2, and 18.3 caused similar increases; however, 18:1 caused the highest rates of triglyceride synthesis. Oleic acid (18:1) was used to further study the secretion of lipoproteins of density less than 1.006 g/ml by CaCo-2 cells. There was a step-wise increase in cellular triglyceride synthesis with increasing oleic acid concentration. Above 250 microM of the fatty acid, however, newly synthesized triglyceride secretion in triglyceride-rich lipoproteins plateaued, suggesting saturation of the secretory pathway. After stimulating triglyceride synthesis by oleic acid, radiolabeled triglyceride secreted in triglyceride-rich lipoproteins was initially delayed resulting in a sigmoid-shaped curve for secretion. This was most pronounced in control cells, which were not incubated with the fatty acid. Over 6 hr, cells incubated with oleic acid secreted more newly synthesized triglyceride in triglyceride-rich lipoproteins compared to control cells. The secretion of lipoproteins of density less than 1.006 g/ml was dependent upon protein synthesis and normal microtubular function in as much as cycloheximide and colchicine significantly decreased triglyceride transport without changing cellular triglyceride synthesis. Triglyceride and unesterified cholesterol mass in lipoproteins of density less than 1.006 g/ml were increased 57 and 244%, respectively, in medium from cells incubated with oleic acid compared to control cells. By 24 hr, 0.17% of lipoproteins of density less than 1.006 g/ml were taken up and degraded. Over the same period, approximately 50% of the lipoprotein triglyceride was hydrolyzed. Under conditions whereby lipoprotein secretion was stimulated fourfold by oleic acid, the activities of HMG-CoA reductase and ACAT were unchanged from activities in control cells. The data suggest that CaCo-2 cells secrete triglyceride-rich lipoproteins of density less than 1.006 g/ml in response to fatty acids in the medium. Triglyceride-rich lipoprotein secretion is a saturable process and dependent on protein synthesis and normal microtubular function. An increase in triglyceride-rich lipoprotein secretion is accompanied by an increase in triglyceride mass in lipoproteins of density less than 1.006 g/ml. By 24 hr, significant postsecretory