黄连素抑制FSP27基因表达及改善T2DM地鼠内脏白色脂肪组织胰岛素抵抗的研究

The investigation on the inhibitive effect of berberine on gene expression of FSP27 to improve visceral white adipose tissue insulin resistance in type 2 diabetic hamsters

目的研究黄连素(BBR)对2型糖尿病(T2DM)中国地鼠内脏白色脂肪组织(VWAT)中脂肪特异蛋白27(FSP27)和PR结构域蛋白16(PRDM16)信号通路基因m RNA表达的影响并探讨相关机制。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佐菌素建立T2DM地鼠模型,对照组喂以普通饲料。造模完成后随机分成对照组、OIR组、肥胖T2DM组和T2DM BBR组。BBR治疗9周后,应用实时定量PCR方法检测各组地鼠VWAT中FSP27和PRDM16信号通路及其靶基因的m RNA表达改变。结果与对照组相比,OIR组和肥胖T2DM组地鼠VWAT中PRDM16、Ct BP-1、Ct BP-2、C/EBPβ、PPARγ、PGC1α、PGC-1β及棕脂组织特异基因UCP-1、Cidea、Elovl3、PPARα及Acox、Cpt1和Acadm的m RNA表达降低,而FSP27和白脂组织特异基因Resistin、MEST和Serpina3k的m RNA表达增加。BBR治疗降低肥胖T2DM组地鼠VWAT中FSP27的表达而增强PRDM16信号通路效应,诱导棕脂组织特异基因m RNA的表达,诱导VWAT棕色化基因表型,改善脂诱性胰岛素抵抗。结论 BBR降低FSP27表达而增加PRDM16的表达与其诱导VWAT棕色化的分子机制相关,有助于增强产热耗能,改善VWAT的异常脂代谢,改善脂诱性VWAT胰岛素抵抗,恢复VWAT的功能。

Objective To study the effects of berberine（BBR） on the gene m RNA expression of fat-specific protein 27（FSP27） and PR domain containing 16（PRDM16） signal pathway in visceral white adipose tissues（VWAT） from type 2 diabetic（T2DM） Chinese hamsters, and explore the related mechanisms. Methods The obese insulin-resistant（OIR） hamstermodel was induced by high-fat diet, and T2DM hamster model was created by OIR hamster model injected with low-dosestreptozotocin. The control group was fed with standard laboratory chow. After the induction, the hamsters were randomly di-vided into control, OIR, obese T2DM and BBR-treated T2DM groups. After nine-week BBR treatment, real-time quantita-tive PCR was used to measure the gene m RNA expression changes of VWAT FSP27 and PRDM16 signal pathway and theirtarget genes from different groups. Results Compared with control group, the gene m RNA expressions of PRDM16, Ct BP-1, Ct BP-2, C/EBPβ, PPARγ, PGC1α, PGC-1β and brown adipose tissue-specific genes such as UCP-1, Cidea, Elovl3,PPARα, and Acox, Cpt1 and Acadm were decreased and that of FSP27 and white adipose tissue-specific genes includingResistin, MEST and Serpina3 k were increased in VWAT in OIR and obese T2DM groups. BBR treatment down-regulatedFSP27 expression, enhanced PRDM16 signal pathway, and induced the gene m RNA expression of brown adipose tissue-spe-cific genes in VWAT of obese T2DM group to develop browning gene phenotype of VWAT, and then improved fat-inducedinsulin resistance. Conclusion The decreased FSP27 expression and increased PRDM16 expression are involved in themolecular mechanisms of browning of visceral white adipose tissues induced by BBR, and which contributes to improve ab-normal lipids metabolism and fat-induced insulin resistance in VWAT by enhancing consumption of energy as heat to re-store VWAT function.