FoxO1对肝脏脂代谢的影响
首发时间:2016-01-21
摘要:FoxO1是叉头转录家族O亚族的一员,因其对胰岛素作用起重要的调控作用而被人所熟知,越来越多的研究表明,FoxO1对于肝脏脂质代谢也起重要的调控作用,其作用机制可能是通过上调微粒体甘油三酯转运蛋白(MTP)、载脂蛋白B(ApoB)的表达,从而促进极低密度脂蛋白(VLDL)在肝脏中的合成,增加循环中VLDL含量;FoxO1还可通过促进载脂蛋白CⅢ(ApoCⅢ)的表达,进而抑制脂蛋白酯酶(LPL)活性,减少循环中甘油三酯(TG)分解,导致高甘油三脂血症的发生;同时,FoxO1还能抑制固醇调节元件结合蛋白SREBP-1c表达,抑制脂肪合成。总之FoxO1活性增强可引起循环中过量的VLDL和TG,进而引起代谢综合征的发生;特异性抑制肝脏FoxO1活性可以减少VLDL-TG的产生,改善糖脂代谢。因此体内靶向抑制FoxO1活性药物的研发可能对于临床上糖尿病血脂异常的具有重要的治疗价值和临床意义。
关键词: FoxO1 甘油三脂 极低密度脂蛋白 微粒体甘油三酯转运蛋白
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The effect of FoxO1 on hepatic lipid metabolism
Abstract:FoxO1 is a member of the FoxO family of transcription factor and is known of it's important role in insulin action. More and more studies have shown that FoxO1 also plays an important role in liver lipid metabolism. The mechanism may be that Foxo1 up-regulated microsomal triglyceride transfer protein (MTP) and Apolipoprotein B(Apo B) expression, promoting the synthesis of VLDL; and also promoting the expression of Apolipoprotein CⅢ(Apo CⅢ), inhibition the activity of lipoprotein lipase (LPL), thereby reducing triglyceride decomposition; FoxO1 can also inhibit SREBP-1c expression, inhibit fat synthesis. In conclusion, enhanced FoxO1 activity can cause excessive circulating VLDL and TG, which can lead to the occurrence of metabolic syndrome. Specific inhibition of the activity of FoxO1 in liver can reduce the production of VLDL-TG and improve glucose and lipid metabolism. Therefore, the research and development of targeted inhibition of FoxO1 activity in vivo may have important therapeutic value and clinical significance for the clinical treatment of dyslipidemia.
Keywords: FoxO1;Triglycerides;very low-density lipoprotein;microsomal triglyceride transfer protein
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