雄激素缺乏对高脂高胆固醇饲喂小型猪肝脏mRNA可变剪接的影响
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1. 浙江省自然科学基金项目(编号:LY18C040003);2. 国家自然科学基金项目(编号:31200921)


Testosterone deficiency regulates mRNA alternative splicing in the liver of miniature pigs fed a high-fat and high-cholesterol diet
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1. Zhejiang Provincial Natural Science Foundation of China (No.LY18C040003); 2. National Natural Science Foundation of China (No. 31200921)

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    摘要:

    [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)小型猪肝脏表达谱,探讨雄激素缺乏对高脂高胆固醇饲喂小型猪肝脏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小型猪肝脏表达谱进行测序,使用TopHat软件筛选三组小型猪肝脏中差异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)去势和睾酮处理可导致高脂高胆固醇饲喂小型猪肝脏mRNA可变剪接发生变化;(2)SHAM vs.CAS和CAS T vs.CAS之间的共有差异AS基因为113个,其中包括AGPAT6、NR1H4、PPARD和GK等与糖脂代谢有关的基因;(3)通过GO和KEGG分析,发现上述共有差异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 雄激素缺乏能够改变高脂高胆固醇饲喂小型猪肝脏mRNA可变剪接,可能会影响肝脏糖脂代谢过程进而促进高脂诱导的NAFLD发病,今后需要对雄激素和上述AS基因之间的关系以及由可变剪接形成新转录本的功能进行进一步研究。

    Abstract:

    Methods We employed the RNA-Seq analysis 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). TopHat was used to identify 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 differential expressed AS genes between three groups. Results (1) Castration and testosterone treatment can introduce new mRNA alternative splicing events in the liver of miniature pigs fed a HFC. (2) There are 113 common differential 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、NR1H4、PPARD and GK. (3) According to GO and KEGG analysis, we found that the 113 genes mainly enriched in fatty acid metabolic process, glycerolipid metabolism, response 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 NAFLD 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.

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蔡兆伟,吕建敏,凌云,黄俊杰,刘军平,潘永明.雄激素缺乏对高脂高胆固醇饲喂小型猪肝脏mRNA可变剪接的影响[J].中国实验动物学报,,().

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  • 收稿日期:2018-03-15
  • 最后修改日期:2018-05-02
  • 录用日期:2018-05-24
  • 在线发布日期: 2018-11-12
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