Chae Sook In, Yi Sang Ah, Nam Ki Hong, Park Kyoung Jin, Yun Jihye, Kim Ki Hyun, Lee Jaecheol, Han Jeung-Whan
School of Pharmacy, Sungkyunkwan University, Suwon 16419, Korea.
Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea.
Molecules. 2020 Dec 13;25(24):5910. doi: 10.3390/molecules25245910.
Obesity causes a wide range of metabolic diseases including diabetes, cardiovascular disease, and kidney disease. Thus, plenty of studies have attempted to discover naturally derived compounds displaying anti-obesity effects. In this study, we evaluated the inhibitory effects of morolic acid 3--caffeate (MAOC), extracted from , on adipogenesis. Treatment of 3T3-L1 cells with MAOC during adipogenesis significantly reduced lipid accumulation and decreased the expression of adiponectin, a marker of mature adipocytes. Moreover, the treatment with MAOC only during the early phase (day 0-2) sufficiently inhibited adipogenesis, comparable with the inhibitory effects observed following MAOC treatment during the whole processes of adipogenesis. In the early phase of adipogenesis, the expression level of which inhibits adipogenesis, increased by MAOC treatment in 3T3-L1 cells. To identify the gene regulatory mechanism, we assessed alterations in histone modifications upon MAOC treatment. Both global and local levels on the promoter region of histone H3 lysine 4 trimethylation, an active transcriptional histone marker, increased markedly by MAOC treatment in 3T3-L1 cells. Our findings identified an epigenetic event associated with inhibition of adipocyte generation by MAOC, suggesting its potential as an efficient therapeutic compound to cure obesity and metabolic diseases.
肥胖会引发多种代谢性疾病，包括糖尿病、心血管疾病和肾脏疾病。因此，大量研究试图发现具有抗肥胖作用的天然衍生化合物。在本研究中，我们评估了从[具体来源未给出]中提取的莫罗酸3 - 咖啡酸酯（MAOC）对脂肪生成的抑制作用。在脂肪生成过程中用MAOC处理3T3 - L1细胞，显著减少了脂质积累，并降低了成熟脂肪细胞标志物脂联素的表达。此外，仅在早期阶段（第0 - 2天）用MAOC处理就足以抑制脂肪生成，这与在脂肪生成全过程中用MAOC处理所观察到的抑制效果相当。在脂肪生成的早期阶段，3T3 - L1细胞中经MAOC处理后，抑制脂肪生成的[具体基因未给出]表达水平升高。为了确定基因调控机制，我们评估了MAOC处理后组蛋白修饰的变化。在3T3 - L1细胞中，经MAOC处理后，组蛋白H3赖氨酸4三甲基化（一种活跃的转录组蛋白标志物）的启动子区域的整体和局部水平均显著增加。我们的研究结果确定了与MAOC抑制脂肪细胞生成相关的表观遗传事件，表明其作为治疗肥胖和代谢性疾病的有效治疗化合物的潜力。
