Abstract：
Sesamolin, a lignan isolated from sesame oils, has been found to possess neuroprotective, anticancer, and free radical scavenging properties. We hypothesized that sesamolin could stimulate the activity of nuclear factor erythroid-derived 2-like 2 (Nrf2) and inhibit adipocyte differentiation of preadipocytes. The objective of this study was to investigate effects of sesamolin on adipocyte differentiation and its underlying molecular mechanisms. In this study, we determined the effects of treatment with 25 to 100 µM sesamolin on adipogenesis in cell culture systems. Sesamolin inhibited lipid accumulation and suppressed the expression of adipocyte markers during adipocyte differentiation of C3H10T1/2, 3T3-L1, and primary preadipocytes. Mechanism studies revealed that sesamolin increased Nrf2 protein expression without inducing its mRNA, leading to an increase in the expression of Nrf2 target genes such as heme oxygenase 1 and NAD(P)H:quinone oxidoreductase 1 (Nqo1) in C3H10T1/2 adipocytes and mouse embryonic fibroblasts. These effects were significantly attenuated in Nrf2 knockout (KO) mouse embryonic fibroblasts, indicating that effects of sesamolin were dependent on Nrf2. In H1299 human lung cancer cells with KO of Kelch like-ECH-associated protein 1 (Keap1), a negative regulator of Nrf2, sesamolin failed to further increase Nrf2 protein expression. However, upon reexpressing Keap1 in Keap1 KO cells, the ability of sesamolin to elevate Nrf2 protein expression was restored, highlighting the crucial role of Keap1 in sesamolin-induced Nrf2 activation. Taken together, these findings show that sesamolin can inhibit adipocyte differentiation through Keap1-mediated Nrf2 activation.
摘要：
塞萨莫林,一种从芝麻油中分离出来的木酚素，被发现具有神经保护作用，抗癌，和自由基清除性能。我们假设芝麻素可以刺激核因子红系衍生的2样2（Nrf2）的活性并抑制前脂肪细胞的脂肪细胞分化。本研究的目的是研究芝麻素对脂肪细胞分化的影响及其潜在的分子机制。在这项研究中,我们确定了用25至100µM芝麻素处理对细胞培养系统中脂肪生成的影响。Sesamolin在C3H10T1/2、3T3-L1和原代前脂肪细胞的脂肪细胞分化过程中抑制脂质积累并抑制脂肪细胞标志物的表达。机制研究表明，芝麻素增加Nrf2蛋白表达而不诱导其mRNA表达，导致Nrf2靶基因如血红素加氧酶1和NAD(P)H:醌氧化还原酶1(Nqo1)在C3H10T1/2脂肪细胞和小鼠胚胎成纤维细胞中的表达增加。这些效应在Nrf2敲除（KO）小鼠胚胎成纤维细胞中显著减弱，表明芝麻素的作用依赖于Nrf2。在具有Kelch样ECH相关蛋白1（Keap1）KO的H1299人肺癌细胞中，Nrf2的负调节因子芝麻素不能进一步增加Nrf2蛋白的表达。然而,在Keap1KO细胞中重新表达Keap1后，芝麻素提高Nrf2蛋白表达的能力得到恢复，强调Keap1在芝麻素诱导的Nrf2激活中的关键作用。一起来看,这些发现表明芝麻素可以通过Keap1介导的Nrf2激活来抑制脂肪细胞的分化。
