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

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。

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

OBJECTIVE To investigate effects of berberine (BBR) on gene mRNA expression of receptor-interacting protein 140 (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 OT2DM hamster models were induced by OIR hamster models injected with low-dose streptozotocin (STZ). Then hamsters were randomly divided into control, OIR, OT2DM and BBR-treated OT2DM 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 Serpina3k 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 PPARα decreased 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 OT2DM hamsters.