雄激素缺乏对高脂高胆固醇饲喂小型猪肝mRNA可变剪接的影响  

Testosterone deficiency regulates mRNA alternative splicing in the liver of miniature pigs fed a high-fat and high-cholesterol diet

作　　者：蔡兆伟[1] 吕建敏 凌云[1] 黄俊杰 刘军平[1] 潘永明[1] CAI Zhaowei;LYU Jianmin;LING Yun;HUANG Junjie;LIU Junping;PAN Yongming(Laboratory /Animal Research Center/Institute of Comparative Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,China)

机构地区：[1]浙江中医药大学动物实验研究中心/比较医学研究所,杭州310053

出　　处：《中国实验动物学报》2018年第4期424-430,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：浙江省自然科学基金项目(No.LY18C040003);国家自然科学基金项目(No.31200921)~~

摘　　要：目的通过分析高脂高胆固醇饲喂的不去势(SHAM)、去势(CAS)和去势+睾酮处理(CAS+T)小型猪肝表达谱,探讨雄激素缺乏对高脂高胆固醇饲喂小型猪肝mRNA可变剪接(alternative splicing,AS)的影响。方法利用转录组测序(RNA-Seq)技术对SHAM、CAS和CAS+T小型猪肝表达谱进行测序,使用Top Hat软件筛选三组小型猪肝中差异AS基因,并对三组样本中共有的差异AS基因进行基因注释和代谢通路富集分析。结果(1)去势和睾酮处理能够引起高脂高胆固醇饲喂小型猪肝mRNA可变剪接发生变化;(2)SHAM vs.CAS和CAS+T vs.CAS之间有113个共有差异AS基因,其中包括AGPAT6、NR1H4、PPARD和GK等糖脂代谢有关基因;(3)GO和KEGG分析结果表明,上述113个差异AS基因主要参与脂肪酸代谢、甘油酯代谢、葡萄糖反应以及脂肪细胞因子信号等生物学过程和通路。结论雄激素缺乏可导致高脂高胆固醇饲喂小型猪肝mRNA可变剪接发生改变,并且可能通过调控肝糖脂代谢进而影响高脂诱导的脂肪肝发病。Objective The aim of this study was to explore the effect of testosterone deficiency on mRNA alternative splicing in the liver of miniature pigs fed a high-fat and high-cholesterol diet（ HFC）. Methods RNA-Seq analysis was employed to characterize the global transcriptome changes in the liver of intact male pigs（ SHAM）,castrated male pigs（ CAS） and castrated male pigs with testosterone treatment（ CAS ＋ T）. Top Hat was used to identify the testosterone-regulated alternative splicing（ AS） events. After being annotated, Gene Ontology（ GO） and Kyoto Encyclopedia of Genes and Genomes（ KEGG） pathway enrichment analyses were further performed for the identified common differentially expressed AS genes between the three groups. Results 1） Castration and testosterone treatment introduced new mRNA alternative splicing events in the liver of miniature pigs fed a HFC. 2） There were 113 common differentially expressed AS genes between SHAM vs. CAS and CAS ＋ T vs. CAS groups,which including many lipid and glucose metabolism-related genes,i. e.,AGPAT6,NR1 H4,PPARD and GK. 3） According to the GO and KEGG analysis,the 113 genes mainly enriched in fatty acid metabolic process,glycerolipid metabolism,responsed to glucose and adipocytokine signaling pathway. Conclusions Testosterone deficiency affects mRNA alternative splicing in the liver of miniature pigs fed a HFC. Moreover,testosterone deficiency may promote diet-induced fatty liver disease through regulating the alternative splicing of genes involved in lipid and glucose metabolism. Further study is needed to explore the relationship between testosterone and the AS genes and their new transcripts.

关 键 词：雄激素 小型猪 脂肪肝 可变剪接 糖脂代谢 

分 类 号：Q95-33[生物学—动物学]