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靶向 FoxO1治疗代谢综合症的潜在意义

     

摘要

Hypertriglyceridemia , a prominent metabolic disease , is believed to play an important part in the development of atherosclerosis and coronary artery disease .Preclinical studies show that FoxO 1 can effectively control insulin-dependent regulation of microsomal triglyceride transfer protein ( MTP ) and apolipoprotein C-Ⅲ ( ApoC-Ⅲ) .Under physiological conditions, FoxO1 activity can be inhibited by insulin.In insulin resistant states, FoxO1 becomes deregulated, contributing to unbridled FoxO1 activity in the liver.This effect contributes to hepatic overproduction of VLDL and impaired catabolism of triglyceride-rich particles, accounting for the pathogenesis of HTG .These data spur the hypothesis that selective inhibition of FoxO1 activity in the liver would improve triglyceride metabolism and ameliorate HTG .In this article, we review the role of FoxO1 in insulin action and lipid metabolism , and evaluate the potential therapeutic value of targeting FoxO1 for treating HTG .%高甘油三酯血症( Hypertriglyceridemia ,HTG)是一种重要的代谢综合征,导致动脉粥样硬化和冠状动脉疾病。FoxO1对调控胰岛素依赖调节的微粒体甘油三酸酯转运蛋白( Microsomal Riglyceride Transfer Protein ,MTP)和载脂蛋白C-III( Apolipoprotein C-III,ApoC-III)有重要作用。文章综述了FoxO1在胰岛素调节和脂类代谢中的作用,并评估利用靶向FoxO1治疗HTG的可能性。

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