Kim H J, Takahashi M, Ezaki O
Division of Clinical Nutrition, National Institute of Health and Nutrition, 1-23-1 Toyama, Shinjuku-ku, Tokyo 162-8636, Japan.
J Biol Chem. 1999 Sep 3;274(36):25892-8. doi: 10.1074/jbc.274.36.25892.
Dietary fish oil induces hepatic peroxisomal and microsomal fatty acid oxidation by peroxisome proliferator-activator receptor alpha activation, whereas it down-regulates 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-1. These data suggested that in liver, fish oil feeding down-regulates the mature form of SREBP-1 by decreasing SREBP-1c mRNA expression, with corresponding decreases of mRNAs of cholesterologenic and lipogenic enzymes.
膳食鱼油通过激活过氧化物酶体增殖物激活受体α诱导肝脏过氧化物酶体和微粒体脂肪酸氧化，而其通过未知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，因此研究了喂食鱼油对C57BL/6J小鼠中SREBPs和固醇调节元件（SRE）依赖性基因表达的影响。三种形式的SREBPs，即SREBP-1a、-1c和-2在肝脏中表达，其截短的成熟形式可激活固醇调节基因的转录。将C57BL/6J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（占总能量的60%），脂肪形式为红花油或鱼油，持续5个月。与喂食红花油相比，喂食鱼油可降低肝脏中的甘油三酯和胆固醇浓度。在喂食碳水化合物和红花油的小鼠之间，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，喂食鱼油可使膜组分中前体SREBP-1的量减少90%，肝脏细胞核中成熟SREBP-1的量减少57%。喂食鱼油还可使前体SREBP-2减少65%，但不改变成熟SREBP-2的量。与喂食红花油相比，喂食鱼油可使肝脏SREBP-1c mRNA水平降低86%，但不改变SERBP-1a mRNA。与成熟SREBP-
