妊娠早期和晚期棕色脂肪组织代谢能力与基因表达变化  

Changes in metabolic capacity and gene expression of brown adipose tissue in the first and third trimester of pregnancy

作　　者：肖文[1] 潘怡慧 仲红 崔县伟[2] Xiao Wen;Pan Yihui;Zhong Hong;Cui Xianwei(Jiangsu Second Normal University,Nanjing 211200,China;Maternaity Hospital Affiliated to Nanjing Medical University(Nanjing Maternal and Child Health Hospital),Medical Research Center,Nanjing 210004,China)

机构地区：[1]江苏第二师范学院,南京211200 [2]南京医科大学附属妇产医院(南京市妇幼保健院)医学研究中心,210004

出　　处：《中华内分泌代谢杂志》2023年第7期588-595,共8页Chinese Journal of Endocrinology and Metabolism

基　　金：国家自然科学基金(82070879)。

摘　　要：目的探究不同妊娠时期棕色脂肪组织(brown adipose tissue, BAT)的基因表达及代谢能力变化。方法建立C57BL/6J小鼠正常妊娠动物模型, 以同周龄未妊娠小鼠为对照组, 观察妊娠各时期BAT组织形态变化, 检测产热标志物解偶联蛋白1(UCP1)表达, 揭示脂肪棕色化及线粒体标志基因的mRNA水平变化;此外选取妊娠早期和晚期小鼠BAT进行转录组测序(RNA sequencing, RNA-seq), 筛选随妊娠进程的差异表达基因, 并开展基因本体(gene ontology, GO)和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)分析。结果随妊娠进展, BAT脂滴显著增大, 产热标志蛋白UCP1表达下降(P<0.01), 脂肪棕色化标志基因Ucp1、2型脱碘酶(Dio2)、过氧化物酶增殖体激活受体γ辅激活因子1α(Pgc1α)以及线粒体标志基因细胞色素C(CytC)均显著下调(P<0.001), 以妊娠晚期组减弱最为显著。RNA-seq共筛选出差异表达基因1 298个, 其中906个基因在妊娠晚期上调、392个基因下调, GO及KEGG通路分析显示差异表达基因在脂质代谢、性类固醇激素、炎症因子等多种生物调节功能通路富集。结论小鼠妊娠晚期BAT出现脂滴变大、产热活性与代谢能力降低现象, BAT基因表达在妊娠不同时期存在显著差异, 因此BAT代谢能力降低可能是引发妊娠期代谢异常的重要原因。Objective To explore gene expression and metabolic capacity changes of brown adipose tissue(BAT)during different gestation periods.Methods A normal pregnancy model was established using C57BL/6J mice,while infertile mice of the same age were served as the control group.The morphological alteration of BAT during pregnancy as well as the gene expression of uncoupling protein 1(UCP1)and other fat browning and mitochondrial marker genes were detected.Moreover,BATs from early and late gestation were selected to screen differentially expressed genes in relation to pregnancy progressing by RNA sequencing(RNA-seq),and gene ontology(GO)and Kyoto gene and gene sequencing(KEGG)were performed.Results With pregnancy progressing,the size of BAT lipid droplets was substantially enlarged,UCP1 protein expression was decreased(P<0.01),and the fat browning marker genes(Ucp1,Dio2,and Pgc1α)and the mitochondrial marker gene CytC were downregulated(P<0.001).Additionally,a total of 1298 distinct genes were identified by RNA-seq,906 of which were upregulated and 392 were downregulated at later stage of pregnancy.GO and KEGG analyses revealed that the differentially expressed genes were mainly enriched in bioregulatory functional pathways such as lipid metabolism,sex steroid hormones,and inflammatory factors.Conclusion BAT in mice showed larger lipid droplets and reduced thermogenic and metabolic capacity during late gestation,and BAT gene expression was significantly different in different periods of gestation,so reduced metabolic capacity of BAT may contribute to metabolic abnormality during pregnancy.

关 键 词：妊娠 棕色脂肪 RNA测序 能量代谢 

分 类 号：R714.256[医药卫生—妇产科学]