Dietary fish oil up-regulates cholesterol 7α-hydroxylase mRNA in mouse liver leading to an increase in bile acid and cholesterol excretion
Dietary fish oil up-regulates cholesterol 7α-hydroxylase mRNA in mouse liver leading to an increase in bile acid and cholesterol excretion
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DOI：
10.1016/s0014-5793(04)00049-3
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发表时间：
2004-02-13
期刊：
影响因子：
3.5
通讯作者：
Darmon, M
中科院分区：
文献类型：
--
作者：
Bérard, AM;Dumon, MF;Darmon, M
为了研究控制胆固醇逆向转运的分子事件，我们比较了正常小鼠肝脏和喂食富含长链（LC）omega-3脂肪酸饮食的小鼠肝脏的基因表达。使用cDNA微阵列，我们评估了1176个基因的表达水平，我们发现D-位点结合蛋白（DBP）在LC omega-3脂肪酸丰富饮食的小鼠中比对照组增加了三倍。已知DBP增加胆固醇7 α-羟化酶（C7 α）的转录水平，胆固醇7 α-羟化酶是胆汁酸产生和胆固醇排泄的限速酶，我们发现C7 a mRNA也被LC omega-3脂肪酸上调。此外，肝脏X受体-α，另一种上调C7 α的转录因子，在治疗小鼠的肝脏中增加了三到四倍。另一方面，我们证明了胆汁酸和胆固醇排泄增加了两倍。这些结果表明，LC ω-3脂肪酸在新的终点控制小鼠的胆固醇代谢。(C)2004年由Elsevier B. V.代表欧洲生物化学学会联合会出版。
To investigate the molecular events controlling reverse cholesterol transport, we compared gene expression of normal mouse liver to that of mice fed a long chain (LC) omega-3 fatty acid-enriched diet. Using cDNA microarrays, we assessed expression levels of 1176 genes, and we found that D-site binding protein (DBP) was three-fold increased in mice on a LC omega-3 fatty acid-rich diet compared to controls. DBP is known to increase transcriptional level of cholesterol 7alpha-hydroxylase (C7alpha), the rate-limiting enzyme for bile acid production and cholesterol excretion, and we found that C7a mRNA was also up-regulated by LC omega-3 fatty acids. Moreover, liver X receptor-alpha, another transcription factor up-regulating C7alpha, was three- to four-fold increased in liver of treated mice. On the other hand, we demonstrated that bile acid and cholesterol excretion were two-fold increased. These results show that LC omega-3 fatty acids control cholesterol metabolism in mice at a new endpoint. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.