Octanoate reduces very low-density lipoprotein secretion by decreasing the synthesis of apolipoprotein B in primary cultures of chicken hepatocytes
Octanoate reduces very low-density lipoprotein secretion by decreasing the synthesis of apolipoprotein B in primary cultures of chicken hepatocytes
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DOI：
10.1016/j.bbalip.2005.09.001
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发表时间：
2005-10-15
影响因子：
4.8
通讯作者：
Akiba, Y
中科院分区：
文献类型：
--
作者：
Tachibana, S;Sato, K;Akiba, Y
不同长度和饱和度的脂肪酸对血浆载脂蛋白 B (apoB) 水平的影响不同。为了确定辛酸对极低密度脂蛋白 (VLDL) 分泌影响的机制，将鸡原代肝细胞与脂肪酸-牛血清白蛋白 (BSA) 复合物或单独的 BSA 一起孵育。与仅用 BSA 和棕榈酸盐处理的对照培养物相比，向培养基中添加辛酸盐显着降低了肝细胞的 VLDL-三酰甘油 (TG)、VLDL-胆固醇和 apoB 分泌，但不调节细胞内 TG 积累。然而，在饱和脂肪酸培养物中没有观察到细胞微粒体甘油三酯转移蛋白水平的差异。在脉冲追踪研究中，辛酸处理导致 apoB-100 合成减少，与其促进分泌一致。通过向肝细胞培养物中添加蛋白酶抑制剂 N-乙酰基-亮氨酰-亮氨酰正亮氨酸 (ALLN)，证实了辛酸的这种特征作用。分析表明，添加辛酸的培养物中apoB mRNA的水平低于对照培养物，但辛酸处理后载脂蛋白A-I、脂肪酸合酶和3-羟基-3-甲基戊二酰辅酶A还原酶mRNA的水平没有观察到显着变化。时程研究表明，apoB mRNA 水平降低 50% 需要与辛酸一起孵育 12 小时。我们得出的结论是，辛酸通过特异性下调 apoB 基因表达和随后的 apoB 合成受损来减少 VLDL 分泌，而不是通过调节细胞内 apoB 降解来减少 VLDL 分泌，而细胞内 apoB 降解已知是其他脂肪酸 VLDL 分泌的主要调节目标。 (c) 2005 Elsevier B.V. 保留所有权利。
Fatty acids of varying lengths and saturation differentially affect plasma apolipoprotein B (apoB) levels, To identify the mechanisms underlying the effect of octanoate on very low-density lipoprotein (VLDL) secretion, chicken primary hepatocytes were incubated with either fatty acid-bovine serum albumin (BSA) complexes or BSA alone. Addition of octanoate to culture medium significantly reduced VLDL-triacylglycerol (TG), VLDL-cholesterol and apoB secretion from hepatocytes compared to both control cultures with BSA only and palmitate treatments, but did not modulate intracellular TG accumulation. However, no differences in cellular microsomal triglyceride transfer protein levels were observed in the cultures with saturated fatty acid. In pulse-chase studies, octanoate treatment resulted in reduced apoB-100 synthesis, in agreement with its promotion of secretion. This characteristic effect of octanoate was confirmed by addition of a protease inhibitor, N-acetyl-leucyl-leucylnorleucinal (ALLN), to hepatocyte cultures. Analysis showed that the level of apoB mRNA was lower in cultures supplemented with octanoate than in the control cultures, but no significant changes were observed in the levels or apolipoprotein A-I, fatty acid synthase and 3-hydroxy-3-methylglutaryl-CoA reductase mRNA as a result of octanoate treatment. Time-course studies indicate that a 50% reduction in apoB mRNA levels requires 12 h of incubation with octanoate. We conclude that octanoate reduced VLDL secretion by the specific down-regulation or apoB gene expression and impairment of subsequent synthesis of apoB, not by the modulation of intracellular apoB degradation, which is known to be a major regulatory target of VLDL secretion of other fatty acids. (c) 2005 Elsevier B.V. All rights reserved.