时钟基因调控低氧训练肥胖大鼠白色脂肪组织棕色化  

Clock genes regulate the browning of white fat in obese rats undergoing hypoxia exercise

作　　者：史东子 张华[3] 孟昶 李昕睿 董盼盼 田雪文 王清路 Shi Dongzi;Zhang Hua;Meng Chang;Li Xinrui;Dong Panpan;Tian Xuewen;Wang Qingu(Shandong Scientific Fitness Guidance Center,School of Sports and Health,Shandong Sport University,Jinan 250102,Shandong Province,China;Key Laboratory of Biomedical Engineering&Technology in Shandong Province Universities,Qilu Medical University,Zibo 255300,Shandong Province,China;School of Sports and Health,Guangdong Polytechnic of Science and Technology,Zhuhai 519090,Guangdong Province,China)

机构地区：[1]山东体育学院,山东省科学健身指导中心,山东省济南市250102 [2]齐鲁医药学院,山东省高校生物医学工程技术重点实验室,山东省淄博市255300 [3]广东科学技术职业学院,体育健康学院,广东省珠海市519090

出　　处：《中国组织工程研究》2024年第16期2473-2480,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(31701042),项目负责人:田雪文。

摘　　要：背景:低氧训练可以促进机体脂肪的降解,外界环境变化可影响动物昼夜节律,但昼夜节律变化对脂肪组织棕色化及脂肪降解的调控机制尚不明确。目的:阐明时钟基因对低氧训练大鼠附睾脂肪组织棕色化的调控机制。方法:喂养高脂饲料构建肥胖大鼠模型,造模成功后抽取40只肥胖大鼠随机分为4组,即常氧安静组、低氧安静组、常氧训练组、低氧训练组,每组10只,进行4周的干预。安静组大鼠不实施干预;低氧组大鼠全天生活在氧浓度为13.6%的低氧仓中;训练组第1周为适应性训练,后3周训练速度和时长保持不变。测量肥胖大鼠体质量、体长和肾周脂肪质量;并使用血脂生化检测试剂盒检测肥胖大鼠血清中三酰甘油、总胆固醇、低密度脂蛋白胆固醇以及高密度脂蛋白胆固醇水平;油红O染色观察肝脏脂肪含量变化;苏木精-伊红染色评价各组大鼠附睾脂肪组织棕色化变化;转录组测序技术结合生物信息学分析脂肪组织中转录组水平变化;采用qRT-PCR检测附睾脂肪组织中PGC-1α、Beclin1、KLF2、Perilipin1 mRNA的表达变化情况。结果与结论:①低氧训练干预使营养性肥胖大鼠体质量、脂体比、Lees’s指数、血清总胆固醇、三酰甘油以及低密度脂蛋白胆固醇浓度显著降低(P<0.01),高密度脂蛋白胆固醇浓度显著升高(P<0.01);②油红O染色和苏木精-伊红染色显示,相比于常氧安静组、低氧安静组和常氧训练组,低氧训练更能有效促进大鼠肝脏组织中脂肪动员和附睾旁脂肪组织棕色化;③转录组测序结果显示,低氧训练时钟基因Dbp、Nr1d1、Sik1以及脂肪组织棕色化基因Ppargc1a(PGC-1α)等表达显著上调(P<0.05),而Arntl(Bmal1)显著下调(P<0.05),同时伴随物质代谢相关基因的表达增强;④qRT-PCR结果证实低氧训练时脂肪组织棕色化基因PGC-1α和脂代谢基因Perilipin1表达量均显著升高(P<0.01);⑤结果证实时钟基因�BACKGROUND:Hypoxic exercise can promote the degradation of body fat,and changes in the external environment can affect the circadian rhythm of animals,but the mechanisms by which changes in circadian rhythm regulate adipose tissue browning and fat degradation are unclear.OBJECTIVE:To elucidate the mechanism of clock gene regulation on epididymal adipose tissue Browning in obese rats undergoing hypoxia exercise.METHODS:Forty obese rats were randomly selected and divided into four groups(n=10 per group):normoxic sedentary group,hypoxic sedentary group,normoxic exercise group,and hypoxic exercise group for 4 weeks of intervention.The rats in the sedentary groups were not intervened,while those in the hypoxic groups lived in a hypoxic chamber with an oxygen concentration of 13.6%for the whole day.In the exercise groups,adaptive training was performed in the 1st week,and the speed and length of training remained unchanged for the last 3 weeks.The body mass,body length and perirenal fat mass of obese rats were measured.Serum levels of triacylglycerol,total cholesterol,low-density lipoprotein cholesterol,and high-density lipoprotein cholesterol in obese rats were detected by a biochemical assay kit.Liver fat content was observed by oil red O staining.Hematoxylin-eosin staining was used to evaluate the browning of epididymal adipose tissue of rats in different groups.RNA sequencing combined with bioinformatics analysis was used to analyze transcriptome changes in adipose tissue.The mRNA expressions of PGC-1α,Beclin 1,KLF 2 and Perilipin 1 in epididymal adipose tissue were detected by RT-PCR.RESULTS AND CONCLUSION:Hypoxic exercise intervention significantly decreased body mass,body fat percentage,Lee’s index,serum triacylglycerol,total cholesterol,and low-density lipoprotein cholesterol levels(P<0.01),and significantly increased high-density lipoprotein cholesterol level(P<0.01).Oil red O staining and hematoxylin-eosin staining results showed that hypoxic exercise was more effective in promoting fat mobilization in liv

关 键 词：低氧训练 肥胖大鼠 脂肪棕色化 时钟基因 昼夜节律 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] Q494[生物学—生理学]