Hepatic overexpression of dominant negative Mlx improves metabolic profile in diabetes-prone C57BL/6J mice
Hepatic overexpression of dominant negative Mlx improves metabolic profile in diabetes-prone C57BL/6J mice
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DOI：
10.1016/j.bbrc.2008.12.100
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发表时间：
2009-02-06
影响因子：
3.1
通讯作者：
Horikawa, Yukio
中科院分区：
文献类型：
--
作者：
Iizuka, Katsumi;Takeda, Jun;Horikawa, Yukio
Mix和ChREBP形成异源二聚体，调节肝脏中葡萄糖介导的基因表达。本研究旨在确定使用显性阴性Mlx （dnMlx）是否可以改善代谢综合征。构建了一种携带dnMlx的腺病毒，并在体内和体外测试了dnMlx对脂肪生成的抑制作用。腺病毒在大鼠肝细胞中过表达dnMlx可抑制Chrebp和转酮酶等葡萄糖调节基因的表达，这两个基因在调节Chrebp基因表达中构成了一个正反馈回路。腺病毒在25周龄雄性C57BL/6J小鼠中过表达dnMlx，通过抑制葡萄糖- g -磷酸酶和Elov16 mRNA以及脂质酶的表达，降低肝脏甘油三酯含量，改善葡萄糖耐受不良。综上所述，dnMlx的过表达不仅通过抑制脂肪生成酶的表达，还通过抑制其他重要基因如葡萄糖-6-磷酸糖和Elovl6的表达来改善葡萄糖耐受不良。(C) 2008爱思唯尔公司版权所有。
Mix and ChREBP form a heterodimer to regulate glucose-mediated gene expression in the liver. This study was performed to determine if the metabolic syndrome might be improved using dominant negative Mlx (dnMlx). An adenovirus bearing dnMlx was constructed and used to test the inhibitory effect of dnMlx on lipogenesis both in vitro and in vivo. Adenoviral overexpression of dnMlx in rat hepatocytes inhibited expression of glucose-regulated genes, including Chrebp and Transketolase, which constitute a positive feedback loop in the regulation of Chrebp gene expression. Adenoviral overexpression of dnMlx in 25-week-old male C57BL/6J mice reduced hepatic triglyceride contents and improved glucose intolerance by inhibiting expression of Glucose-G-phosphatase and Elov16 mRNA in addition to lipogenic enzymes. In conclusion, overexpression of dnMlx improves glucose intolerance by inhibiting expression not only of lipogenic enzymes but also other important genes such as Glucose-6-phosphatose and Elovl6. (C) 2008 Elsevier Inc. All rights reserved.