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醉茄素A通过诱导白色脂肪组织褐变抵御高脂饮食诱导的肥胖

Withaferin A protecting against high fat diet induced obesity by inducing white adipose tissue browning

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【作者】 郭冰冰王炳蔚苏志洁张辰雨赵淼王俊博郑瑞茂

【Author】 GUO Bing-bing;WANG Bing-wei;SU Zhi-jie;ZHANG Chen-yu;ZHAO Miao;WANG Jun-bo;ZHENG Rui-mao;Department of Anatomy,Histology and Embryology,School of Basic Medical Sciences,Peking University Health Science Center; Key Laboratory for Neuroscience of Ministry of Education; Key Laboratory for Neuroscience of National Health Commission;

【通讯作者】 郑瑞茂;

【机构】 北京大学医学部基础医学院人体解剖学与组织学胚胎学系国家教育部神经科学重点实验室国家卫生健康委员会神经科学重点实验室

【摘要】 目的探索醉茄素A对高脂饮食诱导肥胖的抵抗作用及其作用机制。方法 8周龄C57BL/6 J小鼠分为醉茄素A组和对照组,每组10只,高脂饮食(HFD)饲养,分别给予醉茄素A或对照溶剂DMSO腹腔注射,每天测量小鼠体重及摄食量。1周后取材,称量小鼠腹股沟白色脂肪(i WAT)、附睾白色脂肪(e WAT)、腹膜后白色脂肪(r WAT)和肩胛间棕色脂肪(BAT)的重量;取i WAT检测褐变相关因子表达水平; HE染色观察i WAT细胞形态变化。结果醉茄素A组小鼠的体重和各部位脂肪组织重量均显著低于对照组,摄食量无明显变化; Real-time PCR显示,醉茄素A组小鼠i WAT中褐变相关基因表达水平显著提高; Western blotting结果表明,醉茄素A组小鼠i WAT中解耦联蛋白1(UCP1)和过氧化物酶体增殖体激活受体γ共激活因子1α(PGC1α)表达明显增加; HE染色与免疫荧光结果显示,醉茄素A组小鼠腹股沟白色脂肪细胞呈现典型褐变特征,如脂肪细胞多腔室化。结论醉茄素A可能通过诱导小鼠白色脂肪组织褐变抵御高脂饮食诱导的肥胖。

【Abstract】 Objective To investigate the protective effect of withaferin A( WA) against high fat diet induced obesity and its associated mechanism. Methods C57 BL/6 J mice at 8-week of age were divided into two groups. The mice were fed with high fat diet( HFD) and were given an intraperitoneal injection of WA or DMSO( solvent control). The body weight and food intake of the mice were monitored. One week later,inguinal white adipose tissue( i WAT),interscapular brown adipose tissue( BAT),epididymal white adipose tissue( e WAT) and retroperitoneal white adipose tissue( r WAT)were collected and weighed. Expression levels of the genes associated with white adipose browning were detected in i WAT.HE staining was applied to observe the morphological changes of i WAT. Results The data showed that body weight and fat weight in WA group were significantly lower than those in the control group,and the food intake was not changed significantly. Real-time PCR analysis showed that the expression level of browning related genes in i WAT of the WA group was significantly increased. The result from Western blotting analysis showed that the protein levels of uncoupling protein 1( UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha( PGC1α) increased significantly in i WAT of the WA group. The typical morphological change of adipose browning,such as the multilocular adipocytes was observed in inguinal white adipose tissue of the mice treated with WA by using HE staining and mmunofluorescence assay.Conclusion Taken together,these observations indicate that withaferin A can protect the mice from high fat diet induced obesity by promoting white adipose tissue browning.

【基金】 国家自然科学基金(81471064,81670779,81870590);北京市自然科学基金(7162097);国家重点研发计划(2017YFC1700402);北京大学优秀青年人才引进计划科研启动基金(BMU20140366)
  • 【文献出处】 解剖学报 ,Acta Anatomica Sinica , 编辑部邮箱 ,2020年04期
  • 【分类号】R589.2
  • 【下载频次】264
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