饥饿状态下HNF4α对MTP的表达调控

Starvation induced MTP expression in part through HNF4α

肝细胞核因子4α(HNF4α)是肝脏中一种重要的转录因子,其参与多个代谢途径的调控.微粒体甘油三酯转运蛋白(MTP)是极低密度脂蛋白装配和分泌过程的限速酶.C57BL/6J小鼠中研究发现,饥饿可以诱导肝细胞MTP基因的表达.在HepG2细胞中进一步证实饥饿可以诱导MTP表达,同时HNF4α表达也显著上升.实验证实MTP是HNF4α的靶基因之一,用腺病毒介导的HNF4α过表达和HNF4α的激动剂均显著提高MTP的表达;HNF4α特异性siRNA抑制HNF4α的表达,MTP的mRNA和蛋白水平相应下调.结果证明,在饥饿状态下可以诱导MTP和HNF4α的表达,MTP的表达量上升是受到HNF4α的转录调控.

Hepatocyte nuclear factor 4α （HNF4α）is an important transcription factor governing the expression of genes involved in multiple metabolic pathways.Microsomal triglyceride transfer protein （MTP）is a rate-limiting enzyme played a role in the assembly and secretion of very low density lipoproteins（VLDLs）.Fasting induces MTP expression in C57BL/6Jmice.In HepG2cells,we further demonstrate that starvation induces MTP expression,meanwhile enhances HNF4αmRNA level.It was found that MTP is an HNF4αtarget gene.Moreover,adenovirus mediated HNF4αoverexpression and HNF4αagonists induce MTP expression in HepG2cells.HNF4αspecific siRNA represses HNF4αand MTP expression.These results suggest that starvation induces MTP expression in part through HNF4α.