BRD4 regulates fructose-inducible lipid accumulation-related genes in the mouse liver

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• 作者：Aki Yamada^a ; Kazue Honma^a ; Kazuki Mochizuki^b ; Toshinao Goda^a ; ^{gouda@u-shizuoka-ken.ac.jp" class="auth_mail" title="E-mail the corresponding author}
• 关键词：BRD4 ; Histone acetylation ; Fructose ; Lipid metabolism ; Liver
• 刊名：Metabolism
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：65
• 期：10
• 页码：1478-1488
• 全文大小：510 K

文摘

Fructose intake induces hepatic steatosis by activating fat synthesis. In this study, we searched for genes that showed acute induction in the livers of mice force-fed with fructose, and examined how this induction is regulated.

Materials/Methods

We identified genes induced at 6 h after the fructose force-feeding using a microarray and quantitative real-time RT-PCR. Histone acetylation and an acetylated histone binding protein bromodomain containing (BRD)4 binding around the fructose-inducible genes were examined using a chromatin immunoprecipitation assay. We examined whether (+)-JQ1, an inhibitor of the binding between the BRD4 and acetylated histones, inhibited the expressions of fructose-inducible genes, histone acetylation and BRD4 binding around the genes.

Results

We identified upregulated genes related to lipid accumulation, such as Cyp8b1, Dak and Plin5, in mice force-fed with fructose compared with those force-fed with glucose. Acetylation of histones H3 and H4, and BRD4 binding around the transcribed region of those fructose-inducible genes, were enhanced by fructose force-feeding. Meanwhile, (+)-JQ1 treatment reduced expressions of fructose-inducible genes, histone acetylation and BRD4 binding around these genes.

Conclusions

Acute induction of genes related to lipid accumulation in the livers of mice force-fed with fructose is associated with the induction of histone acetylation and BRD4 binding around these genes.