Choline's role in maintaining liver function: new evidence for epigenetic mechanisms.
Choline's role in maintaining liver function: new evidence for epigenetic mechanisms.
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DOI：
10.1097/mco.0b013e3283600d46
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发表时间：
2013-05
影响因子：
3.1
通讯作者：
Zeisel SH
中科院分区：
文献类型：
--
作者：
Mehedint MG;Zeisel SH
人类饮食中胆碱含量低会导致脂肪肝和肝损伤。喂食缺乏胆碱和蛋氨酸的饮食的啮齿动物不仅会患上脂肪肝，还会进一步发展为纤维化和肝癌。本综述重点关注胆碱在肝功能中的作用，特别强调表观遗传作用机制。胆碱等甲基供体的膳食摄入会影响 DNA 和组蛋白的甲基化，从而改变基因表达的表观遗传调控。肝脏是发生甲基化反应的主要器官，许多参与脂肪肝、肝纤维化和肝癌发生途径的肝脏基因均受到表观遗传调控。膳食中胆碱的摄入量相差三倍，许多人的基因多态性增加了对胆碱的需求。胆碱是生成 S-腺苷甲硫氨酸所需的重要甲基供体。膳食胆碱摄入量是 DNA 和组蛋白表观遗传标记的重要修饰剂，从而调节与肝功能和功能障碍有关的许多途径的基因表达。
Humans eating diets low in choline develop fatty liver and liver damage. Rodents fed choline–methionine-deficient diets not only develop fatty liver, but also progress to develop fibrosis and hepatocarcinoma. This review focuses on the role of choline in liver function, with special emphasis on the epigenetic mechanisms of action. Dietary intake of methyl donors like choline influences the methylation of DNA and histones, thereby altering the epigenetic regulation of gene expression. The liver is the major organ within which methylation reactions occur, and many of the hepatic genes involved in pathways for the development of fatty liver, hepatic fibrosis, and hepatocarcinomas are epigenetically regulated. Dietary intake of choline varies over a three-fold range and many humans have genetic polymorphisms that increase their demand for choline. Choline is an important methyl donor needed for the generation of S-adenosylmethionine. Dietary choline intake is an important modifier of epigenetic marks on DNA and histones, and thereby modulates the gene expression in many of the pathways involved in liver function and dysfunction.