Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-1c mRNA in mouse liver - A possible mechanism for down-regulation of lipogenic enzyme mRNAs
Fish oil feeding decreases mature sterol regulatory element-binding protein 1 (SREBP-1) by down-regulation of SREBP-1c mRNA in mouse liver - A possible mechanism for down-regulation of lipogenic enzyme mRNAs
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DOI：
10.1074/jbc.274.36.25892
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发表时间：
1999-09-03
影响因子：
4.8
通讯作者：
Ezaki, O
中科院分区：
文献类型：
--
作者：
Kim, HJ;Takahashi, M;Ezaki, O
鱼油通过激活过氧化物酶体增殖物激活物受体α（Peroxisomeproliferator-activatorreceptor alpha）诱导肝脏过氧化物酶体和微粒体脂肪酸氧化，同时通过未知的机制下调脂肪生成基因的表达。由于固醇调节元件结合蛋白（SREBPs）上调脂肪生成基因，因此研究了鱼油对C57 BL/6 J小鼠SREBPs和固醇调节元件（SRE）依赖性基因表达的影响。三种形式的SREBP，SREBP-1a，-1c和-2，在肝脏中表达，其截短的成熟形式激活固醇调节基因的转录。将C57 BL/6 J小鼠分为三组;第一组给予高碳水化合物饮食，另外两组给予高脂肪饮食（总能量的60%），脂肪以红花油或鱼油的形式存在，持续5个月。与红花油相比，鱼油喂养降低了肝脏中甘油三酯和胆固醇的浓度。在碳水化合物和红花油喂养的小鼠之间，前体和成熟形式的SREBP-1和-2的量没有差异。然而，与喂食红花油相比，喂食鱼油使膜组分中的前体SREBP-1的量减少了90%，使肝细胞核中的成熟SREBP-1的量减少了57%。与红花油相比，鱼油喂养使肝脏SREBP-1c mRNA水平降低86%，但没有改变SERBP-1a mRNA水平。与成熟SREBP-1的降低一致，与红花油相比，鱼油喂养下调了肝脏SRE依赖基因的表达，如低密度脂蛋白受体、3-羟基-3-甲基戊二酰辅酶A还原酶、3-羟基-3-甲基戊二酰辅酶A合酶、脂肪酸合酶、乙酰辅酶A羧化酶和硬脂酰辅酶A去饱和酶-1。这些数据表明，在肝脏中，鱼油喂养通过降低SREBP-1c mRNA表达下调SREBP-1的成熟形式，相应地降低胆固醇生成酶和脂肪生成酶的mRNA。
Dietary fish oil induces hepatic peroxisomal and microsomal fatty acid oxidation by peroxisome proliferator-activator receptor alpha activation, whereas it downregulates lipogenic gene expression by unknown mechanism(s), Because sterol regulatory element-binding proteins (SREBPs) up-regulated lipogenic genes, investigation was made on the effects of fish oil feeding on SREBPs and sterol regulatory element (SRE)-dependent gene expression in C57BL/6J mice. Three forms of SREBPs, SREBP-1a, -1c, and -2, are expressed in liver, and their truncated mature forms activate transcription of sterol-regulated genes. C57BL/6J mice were divided into three groups; the first group was given a high carbohydrate diet, and the other two groups were given a high fat diet (60% of total energy), with the fat in the form of safflower oil or fish oil, for 5 months. Compared with safflower oil feeding, fish oil feeding decreased triglyceride and cholesterol concentrations in liver. There were no differences in amount of SREBP-1 and -2 in both precursor and mature forms between carbohydrate- and safflower oil-fed mice. However, compared with safflower oil feeding, fish oil feeding reduced the amounts of precursor SREBP-1 in membrane fraction by 90% and of mature SREBP-1 in liver nuclei by 57%. Fish oil feeding also reduced precursor SREBP-2 by 65% but did not alter the amount of mature SREBP-2, Compared with safflower oil feeding, fish oil feeding decreased liver SREBP-1c mRNA level by 86% but did not alter SERBP-1a mRNA Consistent with decrease of mature SREBP-1, compared with safflower oil feeding, fish oil feeding down-regulated the expression of liver SRE-dependent genes, such as low density lipoprotein receptor, 3-hydroxy-3-methylglutaryl-CoA reductase, 3-hydroxy-3-methylglutaryl-CoA synthase, fatty acid synthase, acetyl-CoA carboxylase, and stearoyl-CoA desaturase-l. These data suggested that in liver, fish oil feeding downregulates the mature form of SREBP-1 by decreasing SREBP-1c mRNA expression, with corresponding decreases of mRNAs of cholesterologenic and lipogenic enzymes.