Xu Zhumei, Ouyang Lingli, Del Castillo-Olivares Antonio, Pandak William M, Gil Gregorio
Department of Biochemistry and Molecular Biology, Medical College of Virginia at Virginia Commonwealth University, Richmond, Virginia 23298-0614, USA.
Biochim Biophys Acta. 2010 Apr;1801(4):473-9. doi: 10.1016/j.bbalip.2009.12.009. Epub 2009 Dec 28.
alpha(1)-Fetoprotein transcription factor (FTF), also known as liver receptor homolog 1 (LRH-1) is highly expressed in the liver and intestine, where it is implicated in the regulation of cholesterol, bile acid and steroid hormone homeostasis. FTF is an important regulator of bile acid metabolism. We show here that FTF plays a key regulatory role in lipid homeostasis including triglyceride and cholesterol homeostasis. FTF deficient mice developed lower levels of serum triglyceride and cholesterol as a result of lower expression of several hepatic FTF target genes. Chenodeoxycholic acid repressed FTF expression resulting in a decrease in serum triglyceride in wild-type mice. The absence of chenodeoxycholic acid-mediated repression in FTF(+/-) mice demonstrated the essential role of FTF in triglyceride metabolism. Taken together, our results identify the nuclear receptor FTF as a central regulator of lipid metabolism.
甲胎蛋白转录因子（FTF），也称为肝脏受体同源物1（LRH - 1），在肝脏和肠道中高度表达，参与胆固醇、胆汁酸和类固醇激素稳态的调节。FTF是胆汁酸代谢的重要调节因子。我们在此表明，FTF在脂质稳态（包括甘油三酯和胆固醇稳态）中起关键调节作用。由于几种肝脏FTF靶基因表达降低，FTF缺陷小鼠的血清甘油三酯和胆固醇水平较低。鹅去氧胆酸抑制FTF表达，导致野生型小鼠血清甘油三酯降低。在FTF(+/-)小鼠中缺乏鹅去氧胆酸介导的抑制作用，证明了FTF在甘油三酯代谢中的重要作用。综上所述，我们的结果确定核受体FTF是脂质代谢的核心调节因子。
