黄连素对2型糖尿病地鼠内脏脂肪组织RIP140调控通路基因mRNA表达的影响

Effects of Berberine on gene mRNA expression of RIP140 regulative pathway in visceral adipose tissues from type 2 diabetic hamsters

目的:研究黄连素(BBR)对肥胖2型糖尿病(OT2DM)中国地鼠内脏白色脂肪组织(VWAT)中受体相互作用蛋白140(Receptor-interacting protein 140,RIP140)/PR结构域蛋白16(PR domain containing 16,PRDM16)信号通路基因mRNA表达的影响及相关机制。方法:以高脂饮食诱导肥胖胰岛素抵抗(OIR)地鼠模型,然后给予小剂量链脲菌素(STZ)建立OT2DM地鼠模型。造模完成后随机分成对照组、OIR组、OT2DM组和OT2DM BBR治疗组。BBR治疗9周,应用real-time RT-PCR技术检测各组地鼠VWAT中RIP140/PRDM16信号通路基因mRNA表达改变。结果:模型地鼠VWAT中RIP140、PKCε、PRMT1、Exportin1和白脂组织特异基因Resistin和Serpina3k的mRNA表达增加,而PRDM16、CtBP-1、CtBP-2、C/EBPβ、PPARγ、PGC-1α、PGC-1β、Gyk、GPDH、AQP7、GLUT4及棕脂组织特异基因UCP-1、Cidea、Elovl3和PPARα的mRNA表达降低。BBR治疗抑制VWAT中RIP140调控通路,诱导PRDM16信号通路,诱导棕脂组织特异基因mRNA的表达,抑制白色脂肪选择性基因的表达,诱导VWAT棕色化,改善脂诱性胰岛素抵抗(FIIR)。结论:RIP140/PRDM16信号通路参与BBR诱导VWAT棕色化的分子机制。

OBJECTIVE To investigate effects of berberine（BBR）on gene mRNA expression of receptor-interacting protein140（RIP140）/PR domain containing 16（PRDM16）signal pathway in visceral white adipose tissues（VWAT）from obese type 2 diabetic（OT2DM）Chinese hamsters and related mechanisms.METHODS Obese insulin-resistant（OIR）hamster models were induced by high-fat diet and OT2 DM hamster models were induced by OIR hamster models injected with low-dose streptozotocin（STZ）.Then hamsters were randomly divided into control,OIR,OT2 DM and BBR-treated OT2 DM groups.After nine-week BBR treatment,gene mRNA expression changes of VWAT RIP140/PRDM16 signal pathway from different groups were measured by using real-time RT-PCR.RESULTS Gene mRNA expression of RIP140,PKCε,PRMT1,Exportin1 and white adipose tissue-specific genes including Resistin and Serpina3 k increased and those of PRDM16,CtBP-1,CtBP-2,C/EBPβ,PPARγ,PGC-1α,PGC-1β,Gyk,GPDH,AQP7,GLUT4 and brown adipose tissue-specific genes such as UCP-1,Cidea,Elovl3 and PPARαdecreased in dysfunctional VWAT from hamster models.BBR treatment inhibited VWAT RIP140 regulative pathway,induced PRDM16 signal pathway and gene mRNA expression of brown adipose tissue-specific genes,inhibited gene mRNA expression of white adipose tissue-specific genes,induced browning of VWAT,alleviated fat-induced insulin resistance（FIIR）.CONCLUSION RIP140/PRDM16 signal pathway involves in inductive molecular mechanisms of BBR on browning of VWAT in OT2 DM hamsters.