Department of Medical System Engineering, Gwangju Institute of Science and Technology, 123 Cheomdan-gwagiro, Buk-gu, Gwangju 500-712, Republic of Korea.
Biochem Biophys Res Commun. 2013 May 10;434(3):455-9. doi: 10.1016/j.bbrc.2013.03.095. Epub 2013 Apr 10.
Although retinoic acid (RA) is well known to inhibit the differentiation of 3T3-L1 cells into adipocytes both in vivo and in vitro, its molecular mechanism is not fully understood. In this report, we investigate the inhibitory mechanism of adipocyte differentiation by RA in 3T3-L1 cells. Because both RA and Wnt are known to inhibit adipogenesis at a common step involving the inhibition of PPAR-γ expression, we focused on the crosstalk between these two signaling pathways. We found that RA treatment resulted in a dramatic inhibition of adipogenesis, especially at an early phase of differentiation, and led to increased β-catenin protein expression. Moreover, RA enhances the transcriptional activity of β-catenin as well as Wnt gene expression during adipogenesis. Taken together, the present study demonstrated that Wnt/β-catenin signaling may be associated with the RA-induced suppression of adipogenesis and may cooperatively inhibit adipocyte differentiation.
虽然维甲酸 (RA) 在体内和体外都能很好地抑制 3T3-L1 细胞向脂肪细胞分化,但它的分子机制尚不完全清楚。在本报告中,我们研究了 RA 在 3T3-L1 细胞中抑制脂肪细胞分化的机制。由于 RA 和 Wnt 都已知在涉及抑制 PPAR-γ 表达的共同步骤上抑制脂肪生成,因此我们专注于这两个信号通路之间的串扰。我们发现 RA 处理导致脂肪生成的明显抑制,特别是在分化的早期阶段,并导致 β-连环蛋白蛋白表达增加。此外,RA 在脂肪生成过程中增强了 β-连环蛋白以及 Wnt 基因表达的转录活性。总之,本研究表明 Wnt/β-连环蛋白信号通路可能与 RA 诱导的脂肪生成抑制有关,并可能协同抑制脂肪细胞分化。