Effect of diosgenin on metabolic dysfunction: Role of ER beta in the regulation of PPAR gamma
Effect of diosgenin on metabolic dysfunction: Role of ER beta in the regulation of PPAR gamma
复制标题
薯蓣皂苷元对代谢功能障碍的影响：ERβ在PPARγ调节中的作用
DOI：
10.1016/j.taap.2015.09.015
复制
发表时间：
2015
影响因子：
3.8
通讯作者：
Hai Chunxu
中科院分区：
文献类型：
--
作者：
Wang Xin;Liu Jun;Long Zi;Sun Quangui;Liu Ying;Wang Lele;Zhang Xiaodi;Hai Chunxu
本研究旨在探讨薯蓣皂苷元（DSG）对代谢紊乱的影响及其可能的分子机制。采用高脂饲料喂养的小鼠和3 T3-L1前脂肪细胞来评价DSG的作用。我们发现，DSG减轻HF饮食喂养小鼠的代谢功能障碍，如通过降低血糖水平和改善葡萄糖和胰岛素耐受不良所证明的。DSG改善氧化应激，减轻体重，脂肪垫，和系统的脂质谱和衰减的脂质积累。DSG通过调节关键因子抑制3 T3-L1脂肪细胞分化，缩小脂肪细胞体积。DSG抑制HF饮食喂养小鼠的分化的3 T3-L1脂肪细胞和脂肪组织中的PPARγ及其靶基因表达。过表达的PPARγ抑制DSG抑制的脂肪细胞分化。DSG可显著增加ERβ在细胞核的表达。抑制ERβ可显著抑制DSG对脂肪细胞分化和PPARγ表达的抑制作用。DSG刺激后，ERβ与RXRα结合，RXRα与PPARγ解离，导致PPARγ转录活性降低。这些数据为DSG抑制脂肪细胞分化的机制提供了新的见解，并证明ERβ对PPARγ表达和活性的调节对于DSG抑制脂肪细胞分化至关重要。
The present study was designed to investigate the effect of diosgenin (DSG) on metabolic dysfunction and to elucidate the possible molecular mechanisms. High fat (HF) diet-fed mice and 3T3-L1 preadipocytes was used to evaluate the effect of DSG. We showed that DSG attenuated metabolic dysfunction in HF diet-fed mice, as evidenced by reduction of blood glucose level and improvement of glucose and insulin intolerance. DSG ameliorated oxidative stress, reduced body weight, fat pads, and systematic lipid profiles and attenuated lipid accumulation. DSG inhibited 3T3-L1 adipocyte differentiation and reduced adipocyte size through regulating key factors. DSG inhibited PPARγ and its target gene expression both in differentiated 3T3-L1 adipocytes and fat tissues in HF diet-fed mice. Overexpression of PPARγ suppressed DSG-inhibited adipocyte differentiation. DSG significantly increased nuclear expression of ERβ. Inhibition of ERβ significantly suppressed DSG-exerted suppression of adipocyte differentiation and PPARγ expression. In response to DSG stimulation, ERβ bound with RXRα and dissociated RXRα from PPARγ, leading to the reduction of transcriptional activity of PPARγ. These data provide new insight into the mechanisms underlying the inhibitory effect of DSG on adipocyte differentiation and demonstrate that ERβ-exerted regulation of PPARγ expression and activity is critical for DSG-inhibited adipocyte differentiation.