FoxO1 and hepatic lipid metabolism.
FoxO1 and hepatic lipid metabolism.
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DOI：
10.1097/mol.0b013e32832b3f4c
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发表时间：
2009-06
影响因子：
4.4
通讯作者：
Dong HH
中科院分区：
文献类型：
--
作者：
Sparks JD;Dong HH
本文综述了近年来关于葡萄糖代谢关键转录因子叉头盒O1（Forkhead box，Fox）在肝脏脂质代谢调控中的研究进展。导致高胆固醇血症的胰岛素失调与肝脏VLDL分泌增加有关。FoxO1与VLDL代谢中的其他调节因子整合在一起。FoxO1的作用是在最近的争议背景下定义的。FoxO1调节微粒体甘油三酯转移蛋白和载脂蛋白（apo）CIII的转录，参与VLDL的肝脏组装和分泌后catenation。Akt的胰岛素活化导致FoxO1的磷酸化，伴随核排斥和转录活性的丧失。降低胰岛素作用增加FoxO1活性，诱导微粒体甘油三酯转移蛋白，有利于VLDL组装，并诱导apoCIII减少外周甘油三酯催化剂。胰岛素抵抗与VLDL过度产生和高胆固醇血症之间的这种新的机制联系与其他已知的VLDL调节因子的作用有关。本文综述了近年来胰岛素对肝脏VLDL代谢调控的研究进展。VLDL的形成需要脂质、apoB结构蛋白和微粒体甘油三酯转移蛋白。FoxO1是肝微粒体甘油三酯转移蛋白调节的主要因子。一个统一的假设，提出了连接调节的三个必要的肝脏成分与胰岛素作用和胰岛素抵抗的极低密度脂蛋白组装。
This review summarizes recent research implicating Forkhead box (Fox)O1, a key transcription factor in glucose metabolism, in the regulation of hepatic lipid metabolism. Insulin dysregulation leading to hypertriglyceridemia is associated with increased hepatic VLDL secretion. FoxO1 is integrated in action with other regulatory factors in VLDL metabolism. The role of FoxO1 is defined in context of recent controversies. FoxO1 regulates transcription of microsomal triglyceride transfer protein and apolipoprotein (apo)CIII involved in hepatic assembly and postsecretory catabolism of VLDL. Insulin activation of Akt leads to the phosphorylation of FoxO1 with nuclear exclusion and loss of transcriptional activity. Reduced insulin action increases FoxO1 activity and induces microsomal triglyceride transfer protein favoring VLDL assembly and induces apoCIII reducing peripheral triglyceride catabolism. This new mechanistic link between insulin resistance and VLDL overproduction and hypertriglyceridemia compounds effects of other known VLDL regulatory factors. This review highlights recent advances in research of insulin regulation of hepatic VLDL metabolism. Formation of VLDL requires lipid, apoB structural protein, and microsomal triglyceride transfer protein. FoxO1 is a major factor in hepatic microsomal triglyceride ransfer protein regulation. A unifying hypothesis is presented linking regulation of the three necessary hepatic components for VLDL assembly with insulin action and insulin resistance.