Department of Food and Nutrition, Yonsei University, Seoul, Republic of Korea.
Int J Obes (Lond). 2013 Jun;37(6):881-4. doi: 10.1038/ijo.2012.158.
Indole-3-carbinol (I3C), a natural product of Brassica vegetables such as broccoli and cabbage, inhibits proliferation and induces apoptosis in various cancer cells. I3C has recently received attention as a possible anti-obesity agent. However, how I3C interacts with specific targets in the pathways involved in obesity and metabolic disorders is unknown. Silent mating type information regulation 2 homolog 1 (SIRT1), a NADþ-dependent deacetylase sirtuin, has recently emerged as a novel therapeutic target for metabolic diseases. Herein, we report that I3C is a potent, specific SIRT1 activator efficacious in cultured 3T3-L1 cell lines. A pull-down assay showed that I3C binds to SIRT1. To assess the significance of this binding, we determined whether I3C could activate SIRT1 deacetylase activity in a cell-free system. We found that I3C binds to SIRT1 and activates SIRT1 deacetylase activity in 3T3-L1 cells. In addition, I3C did not inhibit adipocyte differentiation in 3T3-L1 cells in which SIRT1 was knockdowned. Further, reverse transcriptase polymerase chain reaction analysis showed that I3C treatment reduced mRNA levels of adipogenic genes that encode for C/EBPa, PPARg2, FAS, and aP2 in 3T3-L1 cells but not in SIRT1 knockdown cells. Overall, these results suggested that I3C ameliorates adipogenesis by activating SIRT1 in 3T3-L1 cells.
吲哚-3-甲醇（I3C）是西兰花和白菜等 Brassica 蔬菜中的一种天然产物，能抑制多种癌细胞的增殖并诱导其凋亡。I3C 最近作为一种可能的抗肥胖剂受到关注。然而，I3C 如何与肥胖和代谢紊乱相关途径中的特定靶点相互作用尚不清楚。沉默信息调节因子 2 同源物 1（SIRT1）是一种 NAD+依赖的去乙酰化酶 Sirtuin，最近已成为代谢疾病的一种新的治疗靶点。在此，我们报告 I3C 是一种有效的、特异性的 SIRT1 激活剂，可在培养的 3T3-L1 细胞系中发挥作用。下拉实验表明，I3C 与 SIRT1 结合。为了评估这种结合的意义，我们确定 I3C 是否可以在无细胞系统中激活 SIRT1 的去乙酰化酶活性。我们发现 I3C 与 SIRT1 结合并激活 SIRT1 的去乙酰化酶活性。此外，在 SIRT1 敲低的 3T3-L1 细胞中，I3C 不会抑制脂肪细胞分化。此外，逆转录聚合酶链反应分析显示，I3C 处理可降低编码 C/EBPa、PPARg2、FAS 和 aP2 的脂肪生成基因在 3T3-L1 细胞中的 mRNA 水平，但在 SIRT1 敲低细胞中则没有。总的来说，这些结果表明，I3C 通过在 3T3-L1 细胞中激活 SIRT1 来改善脂肪生成。
