Faculty of Pharmaceutical Science, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Faculty of Pharmaceutical Science, Fukuoka University, 8-19-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
Mol Cell Endocrinol. 2018 Oct 15;474:48-56. doi: 10.1016/j.mce.2018.02.006. Epub 2018 Feb 15.
Fat-specific protein 27 (FSP27) is highly expressed in the fatty liver of genetically obese ob/ob mice and promotes hepatic triglyceride (TG) accumulation. The nuclear hormone receptor liver X receptor α (LXRα) also plays a critical role in the control of TG levels in the liver. The present study demonstrated transcriptional regulation of Fsp27a and Fsp27b genes by LXRα. Treatment with the LXR ligand T0901317 markedly increased Fsp27a and Fsp27b mRNAs in wild-type C57BL/6J and ob/ob mouse livers. A reporter assay indicated that two LXR-responsive elements (LXREs) are necessary for LXRα-dependent induction of Fsp27a and Fsp27b promoter activities. Furthermore, the LXRα/retinoid X receptor α complex is capable of directly binding to the two LXREs both in vitro and in vivo. These results suggest that LXRα positively regulates Fsp27a and Fsp27b expression through two functional LXREs. Fsp27a/b are novel LXR target genes in the ob/ob fatty liver.
脂肪特异性蛋白 27(FSP27)在遗传性肥胖 ob/ob 小鼠的脂肪肝中高度表达,并促进肝甘油三酯(TG)蓄积。核激素受体肝 X 受体α(LXRα)在肝脏 TG 水平的控制中也起着关键作用。本研究证明了 LXRα对 Fsp27a 和 Fsp27b 基因的转录调控。用 LXR 配体 T0901317 处理,野生型 C57BL/6J 和 ob/ob 小鼠肝脏中的 Fsp27a 和 Fsp27b mRNA 明显增加。报告基因检测表明,两个 LXR 反应元件(LXREs)是 LXRα 依赖诱导 Fsp27a 和 Fsp27b 启动子活性所必需的。此外,LXRα/视黄酸 X 受体α 复合物能够在体外和体内直接结合到两个 LXRE 上。这些结果表明,LXRα 通过两个功能性 LXRE 正向调节 Fsp27a 和 Fsp27b 的表达。Fsp27a/b 是 ob/ob 脂肪肝中 LXR 的新靶基因。