人参皂苷Rb2通过抑制自噬促进肥胖小鼠白色脂肪棕色化

Ginsenoside Rb2 induced browning of white fat of obese mice via inhibiting autophagy

目的:探讨人参皂苷Rb2(Rb2)通过调节自噬信号通路,促进肥胖小鼠白色脂肪棕色化的作用。方法:利用高脂喂食建立肥胖小鼠模型,观察Rb2对实验小鼠体重和脂肪质量的影响,利用实时荧光定量PCR和蛋白质印迹法(Western印迹)检测脂肪组织自噬信号通路的表达变化。利用自噬信号通路激动剂雷帕霉素处理3T3-L1脂肪细胞和脂肪来源的基质血管组分,观察激活自噬对棕色化基因表达影响及Rb2干预后是否逆转雷帕霉素的作用。结果:Rb2减轻高脂饮食诱导的肥胖小鼠体重和脂肪质量,抑制自噬相关基因(Atg)5、Atg7、Beclin-1基因和Beclin-1蛋白、微管相关蛋白1轻链3(LC3)-Ⅱ/LC3-Ⅰ的表达,上调p62蛋白的表达,提示Rb2可能通过抑制自噬缓解肥胖。进一步体外实验发现,雷帕霉素处理3T3-L1脂肪细胞,激活自噬并抑制棕色化基因表达,Rb2部分拮抗雷帕霉素对白色脂肪自噬的激活和棕色化的抑制作用。结论:Rb2可以减轻高脂诱导的肥胖小鼠体重,其作用机制可能与抑制脂肪组织自噬信号通路、上调棕色化相关基因表达有关。

Objective To investigate the role of ginsenoside Rb2(Rb2)on promoting the browning of white fat of obese mice via regulating the autophagy signaling pathway.Methods High-fat diet was fed to establish a diet-induced obesity mouse model,the body weight and the fat mass of mice were measured after Rb2 treatment.Quantitative realtime PCR and Western blotting were performed to detect changes in the levels of autophagy in adipose tissues.3T3-L1 adipocytes and stromal vascular fraction derived from adipose tissue were treated with rapamycin,an agonist of autophagy signaling pathway,to investigate the effect of activated autophagy on the expression browning genes and to find whether this effect would be reversed after Rb2 intervention.Results Rb2 significantly reduced body weight and fat mass in obese mice,suppressed the expression of autophagy markers,autophagy related gene(Atg)5,Atg7,Beclin-1,and microtubule-associated protein 1 light chain 3(LC3)-Ⅱ/LC3-Ⅰ,as well enhanced p62 protein expression,while may indicate that Rb2 might alleviate obesity through inhibition of autophagy.Further in vitro experiments,suggested that the treatment of rapamycin in 3T3-L1 adipocytes activated autophagy and suppressed browning gene expression,which was partially antagonized by Rb2.Conclusion Rb2 reduces the body weight of obese mice induced by high fat,and its mechanism may be related to the inhibition of autophagy and the up-regulation of browning gene programs in adipose tissues.