通过BHLHB2/DEC1和ChREBP反馈回路对脂肪生成的调控。
Regulation of lipogenesis via BHLHB2/DEC1 and ChREBP feedback looping.
作者信息
Iizuka Katsumi, Horikawa Yukio
机构信息
Laboratory of Medical Genomics, The Institute for Molecular and Cellular Regulation, Gunma University, Maebashi-shi Gunma 371-8512, Japan.
出版信息
Biochem Biophys Res Commun. 2008 Sep 12;374(1):95-100. doi: 10.1016/j.bbrc.2008.06.101. Epub 2008 Jul 9.
BHLHB2/DEC1 is a transcription factor implicated in cell proliferation, apoptosis, and metabolism, and is also known to play an important role in the regulation of the mammalian circadian rhythm. However, its precise role in metabolism remains unclear. We investigated the link between BHLHB2 and ChREBP, a glucose-activated transcription factor involved in the regulation of lipogenesis. Glucose stimulation and overexpression of dominant active ChREBP induced Bhlhb2 mRNA expression in rat hepatocytes. Deletion studies showed that ChoRE (-160 to -143bp) in the mouse Bhlhb2 promoter region is functional in vivo. Overexpression of BHLHB2 inhibited glucose and ChREBP-mediated induction of rat Fasn and liver pyruvate kinase (Lpk) mRNA. ChIP assay demonstrated that BHLHB2 bound to ChoRE in the Fasn, Lpk, and Bhlhb2 promoter regions in vivo. In conclusion, BHLHB2 and ChREBP constitute a novel feedback loop involved in the regulation of lipogenesis.
BHLHB2/DEC1是一种与细胞增殖、凋亡及代谢相关的转录因子，并且已知其在哺乳动物昼夜节律调节中发挥重要作用。然而，其在代谢中的精确作用仍不清楚。我们研究了BHLHB2与ChREBP（一种参与脂肪生成调节的葡萄糖激活转录因子）之间的联系。葡萄糖刺激及显性活性ChREBP的过表达可诱导大鼠肝细胞中Bhlhb2 mRNA的表达。缺失研究表明，小鼠Bhlhb2启动子区域中的ChoRE（-160至-143bp）在体内具有功能。BHLHB2的过表达抑制了葡萄糖和ChREBP介导的大鼠Fasn和肝丙酮酸激酶（Lpk）mRNA的诱导。染色质免疫沉淀分析表明，BHLHB2在体内与Fasn、Lpk和Bhlhb2启动子区域中的ChoRE结合。总之，BHLHB2和ChREBP构成了一个参与脂肪生成调节的新型反馈环。
Zotero 插件