SND1转基因小鼠改善高脂饮食诱导的脂肪肝和胰岛素抵抗

发布时间：2018-10-29 09:18

【摘要】：研究背景和目的:多功能蛋白SND1可以在转录水平激活脂肪形成相关基因的表达,并且调控脂肪细胞的分化。但是SND1在体内与代谢的关系还不清楚。本研究的目的是检测全身过表达SND1的小鼠对高脂饮食(HFD)诱导的非酒精性脂肪性肝病(NAFLD)和胰岛素敏感性的影响。方法:构建全身过表达SND1蛋白小鼠(SND1-Tg),平行饲养野生型小鼠为对照组。出生8周后,进行高脂饮食(HFD)或正常饮食(CD)饲养,12周后检测肝脏和脂肪的组织学和代谢学表型。肝脏的表达谱芯片用于筛选差异表达的基因,并用qPCR验证,探讨其分子机制。结果:在HFD诱导的NAFLD中,SND1能够激活肝脏中胆固醇和磷脂的合成并促进LDL对肝脏中脂类的运输以及白色脂肪中脂类的从头合成过程,随后减少了肝脏中甘油三酯的堆积和全身的胰岛素敏感。更重要的是,HFD的转基因小鼠表现出肝脏脂肪病变的降低。这很大程度上是由于肝脏中低密度脂蛋白-胆固醇的更高输出,以及白色脂肪细胞分泌了更多的瘦素进入血液并作用于肝脏。潜在的机制可能是由于SND1通过SCAP促进了SREBP2的核定位导致的,核内定位的SREBP2,作为胆固醇合成的关键转录因子促进胆固醇的合成。结论:SND1转基因小鼠促进胆固醇合成并改善非酒精性脂肪肝的脂肪病变和胰岛素抵抗。
[Abstract]:Background & AIM: multifunctional protein SND1 can activate the expression of adipose-associated genes and regulate adipocyte differentiation at the transcriptional level. But the relationship between SND1 and metabolism in vivo is unclear. The aim of this study was to investigate the effects of over expression of SND1 on (NAFLD) and insulin sensitivity in mice with non alcoholic fatty liver disease induced by high fat diet (HFD). Methods: whole body overexpression SND1 protein mice (SND1-Tg) were constructed, and wild type mice were used as control group. After 8 weeks of birth, the liver and fat were fed with high fat diet (HFD) or normal diet (CD), and the histological and metabolic phenotypes of liver and fat were detected after 12 weeks. Liver expression microarray was used to screen differentially expressed genes and its molecular mechanism was investigated by qPCR. Results: in NAFLD induced by HFD, SND1 activated the synthesis of cholesterol and phospholipid in the liver and promoted the transport of lipids by LDL and the ab initio synthesis of lipids in white fats. It then reduces the accumulation of triglycerides in the liver and insulin sensitivity throughout the body. More importantly, HFD transgenic mice showed a decrease in liver fat lesions. This is largely due to higher output of LDL-cholesterol in the liver and more leptin secreted by white fat cells into the blood and acting on the liver. The underlying mechanism may be that SND1 promotes the nuclear localization of SREBP2 through SCAP, and that SREBP2, is a key transcriptional factor in cholesterol synthesis. Conclusion: SND1 transgenic mice promote cholesterol synthesis and improve fatty lesions and insulin resistance in non-alcoholic fatty liver.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R575

【相似文献】