TGR5多种配体抑制高脂饮食小鼠肥胖及高血糖的效果对比研究  

Comparison of the Effects of TGR5 Ligands on Obesity and Hyperglycemia in High Fat Diet Mice

作　　者：陈小松[1] 闫柳[1] 陈瑛[1] 李向禹[1] 郭志辉[1] 李铭[1] 

机构地区：[1]福建医科大学附属协和医院整形外科,福建福州350001

出　　处：《中国美容医学》2017年第7期32-36,共5页Chinese Journal of Aesthetic Medicine

基　　金：国家自然科学基金(No.81372092);国家自然科学基金(No.81671930);福建省科技厅高校产学研合作项目(No.2016Y4003);福建省发改委产业技术联合创新项目(No.02011601);福建省财政专项项目(No.010110002)

摘　　要：目的:本研究通过建立肥胖小鼠动物模型,分析比较胆汁酸膜受体TGR5多种配体的减肥及降糖效果,以筛选出TGR5最佳配体。方法:选取6周龄C57BL/6野生型小鼠,随机分为2组,分别用NF、HF喂养10周后,NF组小鼠采用NF继续喂养10周;将HF组小鼠分为7组,分别用HF、HF+OA(H)、HF+OA(L)、HF+CDCA、HF+CA、HF+DCA、HA+LCA喂养10周。共喂养20周后进行糖耐量实验、测定血清胰岛素水平并取肝脏脂肪组织做病理学观察,RT-PCR法检测脂肪酸合成与脂肪代谢相关基因表达情况。喂养过程中每周监测小鼠体重。结果:TGR5多种配体可激活TGR5调节肥胖小鼠体内糖脂代谢,降低小鼠体重、提高小鼠糖耐量水平,激活脂肪酸合成及氧化相关基因的表达,其中以OA(H)、CDCA和CA作用较为显著。结论:OA(H)、CDCA和CA可有效降低体重、提高糖耐量水平、降低血清胰岛素水平、缓解肝脏脂质沉积及调节脂肪代谢相关基因的表达。Objective To screen out the best ligand by comparing the weight loss and hypoglycemic effects of various ligands for bile acid receptor TGR5 in diet-induced obese mice. Methods Wild-type mice of 6 weeks old were fed with HF or the control regular chow diet for 10 weeks. Then mice fed with HF were randomly divided into seven groups. One group were kept feeding with HF. The other groups were switched to HF＋OA（H）, HF＋OA（L）, HF＋CDCA, HF＋CA, HF＋DCA, HA＋LCA for additional 10 weeks. Glucose tolerance test and serum insulin levels were detected after 20 weeks. Hematoxylin and eosin staining was performed for standard histological examination in liver and adipose tissues. Expression of genes related to glucose metabolism in adipose tissues was measured by Real-time PCR. Mice body weights were monitored during the entire process. Results TGR5 activation by its ligands decreased the body weight, enhanced insulin sensitivity in mice and up- regulated the expression of genes related to fatty acid synthesis and oxidation in adipose tissues, with OA（H）, CDCA and CA affected significantly. Conclusion OA（H）, CDCA and CA were identified as being effective at reducing weight, improving glucose tolerance, reducing serum insulin levels, relieving liver lipid deposition and regulating the expression of fat metabolism related genes.

关 键 词：TGR5配体 褐色脂肪 肥胖 糖脂代谢 

分 类 号：R589.2[医药卫生—内分泌]