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

  • Metabolism. 2016 Oct;65(10):1478-88. doi: 10.1016/j.metabol.2016.07.001.
Aki Yamada  1 ,  Kazue Honma  1 ,  Kazuki Mochizuki  2 ,  Toshinao Goda  3
Affiliations
  • 1. Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences, Laboratory of Nutritional Physiology, University of Shizuoka, Shizuoka, Japan.
  • 2. Laboratory of Food and Nutritional Sciences, Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Yamanashi, Japan.
  • 3. Laboratory of Nutritional Physiology, Graduate School of Nutritional and Environmental Sciences, Laboratory of Nutritional Physiology, University of Shizuoka, Shizuoka, Japan. Electronic address: [email protected].
PMID: 27621183 DOI: 10.1016/j.metabol.2016.07.001
Abstract

Objective: 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 6h 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.

Keywords
BRD4; Fructose; Histone acetylation; Lipid metabolism; Liver.
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