Division of Longevity and Biofunctional Medicine, School of Korean Medicine, Pusan National University, Yangsan-si, Gyeongnam, South Korea.
Healthy Aging Korean Medical Research Center, School of Korean Medicine, Pusan National University, Yangsan-si, Gyeongnam, South Korea.
Sci Rep. 2017 Jan 9;7:40345. doi: 10.1038/srep40345.
Gomisin N (GN) is a physiological lignan derived from Schisandra chinensis. In the present study, we investigated the inhibitory effects of GN on differentiation of 3T3-L1 preadipocytes and the anti-obesity effects of GN in high-fat diet (HFD)-induced obese mice. Incubation with GN significantly inhibited the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner. This inhibitory effect primarily occurred at an early adipogenic stage through impairment of mitotic clonal expansion (MCE) caused by cell cycle arrest at the G1/S phase transition. GN inhibited the extracellular signal-regulated kinase and phosphoinositide 3-kinase/protein kinase B signaling in the MCE process and activated AMP-activated protein kinase. Furthermore, GN downregulated CCAT/enhancer-binding protein β (C/EBPβ) and histone H3K9 demethylase JMJD2B during early stages of adipogenesis, and therefore repressed the expression of C/EBPβ-targeted cell cycle genes. In addition, GN also repressed the expression of histone H3K4 methyltransferase MLL4 and reduced PPARγ expression. Moreover, GN effectively lowered the final body weight, adipose tissue mass, and reduced the serum levels of glucose, total triglyceride, and cholesterol in the HFD-induced obese mice. GN also markedly reduced hepatic triglyceride level induced by HFD. Collectively, these findings suggest that GN has potential as a novel agent for the prevention and treatment of obesity.
戈米辛 N（GN）是一种来源于五味子的生理木质素。在本研究中，我们研究了 GN 对 3T3-L1 前脂肪细胞分化的抑制作用以及 GN 在高脂饮食（HFD）诱导肥胖小鼠中的抗肥胖作用。GN 孵育以剂量依赖性方式显著抑制 3T3-L1 前脂肪细胞的分化。这种抑制作用主要发生在早期脂肪生成阶段，通过细胞周期停滞在 G1/S 转换时引起有丝分裂克隆扩张（MCE）受损。GN 在 MCE 过程中抑制细胞外信号调节激酶和磷脂酰肌醇 3-激酶/蛋白激酶 B 信号通路，并激活 AMP 激活的蛋白激酶。此外，GN 在脂肪生成的早期阶段下调 CCAT/增强子结合蛋白 β（C/EBPβ）和组蛋白 H3K9 去甲基化酶 JMJD2B，从而抑制 C/EBPβ 靶向细胞周期基因的表达。此外，GN 还抑制组蛋白 H3K4 甲基转移酶 MLL4 的表达并降低 PPARγ 的表达。此外，GN 还能有效降低 HFD 诱导肥胖小鼠的最终体重、脂肪组织质量，并降低血清中葡萄糖、总甘油三酯和胆固醇水平。GN 还显著降低 HFD 诱导的肝甘油三酯水平。总之，这些发现表明 GN 具有作为肥胖预防和治疗的新型药物的潜力。
