Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: effect on fatty acid synthesis and triacylglycerol transport
Polyunsaturated fatty acids decrease the expression of sterol regulatory element-binding protein-1 in CaCo-2 cells: effect on fatty acid synthesis and triacylglycerol transport
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DOI：
10.1042/bj20020731
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发表时间：
2002-12-15
影响因子：
4.1
通讯作者：
Mathur, SN
中科院分区：
文献类型：
--
作者：
Field, FJ;Born, E;Mathur, SN
在CaCo-2细胞中研究了脂肪酸流量对固醇调节元件结合蛋白（SREBPs）的调节。将细胞与含有或不含有250 μ M 18：0、18：1、18：2、20：4、20：5或22：6脂肪酸的1mM牛磺胆酸盐一起孵育。脂肪酸合成酶（FAS）和乙酰辅酶A羧化酶的mRNA水平和基因和蛋白质表达的SREBP估计。18：2、20：4、20：5和22：6脂肪酸降低成熟SREBP-1的量以及SREBP-1c、SREBP-1a、FAS和乙酰辅酶A羧化酶的mRNA水平。SREBP-2基因或成熟蛋白表达没有改变。T0901317激活肝脏X受体（LXR）可增加SREBP-1c、SREBP-1a、FAS和乙酰辅酶A羧化酶的基因表达，而不改变SREBP-2。20：5而非18：1抑制了T0901317对SREBP-1c mRNA的完全表达。T0901317增加了SREBP-1的质量，而不改变成熟SREBP-2的质量。虽然只有18：2，20：4，20：5和22：6抑制SREBP-1，乙酰辅酶A羧化酶和FAS的表达，所有的脂肪酸降低脂肪酸的合成速率。T0901317增加内源性脂肪酸合成，但不增加富含三酰甘油脂蛋白的分泌。在CaCo-2细胞中，多不饱和脂肪酸降低SREBP-1和FAS mRNA的基因和蛋白表达，可能是通过干扰LXR活性。由于所有脂肪酸减少脂肪酸合成，机制以外的变化SREBP-1c的表达必须受理。内源性脂肪酸合成增加不会促进富含三酰甘油的脂蛋白分泌。
Regulation of sterol regulatory element-binding proteins (SREBPs) by fatty acid flux was investigated in CaCo-2 cells. Cells were incubated with 1 mM taurocholate with or without 250 muM 18:0, 18:1, 18:2, 20:4, 20:5 or 22:6 fatty acids. Fatty acid synthase (FAS) and acetyl-COA carboxylase mRNA levels and gene and protein expression of SREBPs were estimated. 18:2, 20:4, 20:5 and 22:6 fatty acids decreased the amount of mature SREBP-1 and mRNA levels of SREBP-1c, SREBP-1a, FAS and acetyl-CoA carboxylase. SREBP-2 gene or mature protein expression was not altered. Liver X receptor (LXR) activation by T0901317 increased gene expression of SREBP-1c, SREBP-1a, FAS and acetyl-CoA carboxylase without altering SREBP-2. 20:5, but not 18:1, prevented the full expression of SREBP-1c mRNA by T0901317. T0901317 increased SREBP-1 mass without altering the mass of mature SREBP-2. Although only 18:2, 20:4, 20:5 and 22:6 suppressed SREBP-1, acetyl-CoA carboxylase and FAS expression, all fatty acids decreased the rate of fatty acid synthesis. T0901317 increased endogenous fatty acid synthesis yet did not increase secretion of triacylglycerol-rich lipoproteins. In CaCo-2 cells, polyunsaturated fatty acids decrease gene and protein expression of SREBP-1 and FAS mRNA, probably through interference with LXR activity. Since all fatty acids decreased fatty acid synthesis, mechanisms other than changes in SREBP-1c expression must be entertained. Increased endogenous fatty acid synthesis does not promote triacylglycerol-rich lipoprotein secretion.