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十二指肠-空肠旁路术后回肠长链非编码RNA的改变与脂质和氨基酸代谢的调节有关。

Alteration of Ileal lncRNAs After Duodenal-Jejunal Bypass Is Associated With Regulation of Lipid and Amino Acid Metabolism.

作者信息

Liang Yongjun, Yu Minghua, Wang Yueqian, Li Mengyi, Zhang Zhongtao, Qiao Zhengdong, Zhang Peng

机构信息

Center for Medical Research and Innovation, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

Shanghai Key Laboratory of Vascular Lesions Regulation and Remodeling, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

出版信息

Front Physiol. 2022 Apr 7;13:836918. doi: 10.3389/fphys.2022.836918. eCollection 2022.

Abstract

Metabolic and bariatric surgery (MBS) can generate a drastic shift of coding and noncoding RNA expression patterns in the gastrointestinal system, which triggers organ function remodeling and may induce type 2 diabetes (T2D) remission. Our previous studies have demonstrated that the altered expression profiles of duodenal and jejunal long noncoding RNAs (lncRNAs) after the duodenal-jejunal bypass (DJB), an investigational procedure and research tool of MBS, can improve glycemic control by modulating the entero-pancreatic axis and gut-brain axis, respectively. As an indiscerptible part of the intestine, the ileal lncRNA expression signatures after DJB and the critical pathways associated with postoperative correction of the impaired metabolism need to be investigated too. High-fat diet-induced diabetic mice were randomly assigned into two groups receiving either DJB or sham surgery. Compared to the sham group, 1,425 dysregulated ileal lncRNAs and 552 co-expressed mRNAs were identified in the DJB group. Bioinformatics analysis of the differently expressed mRNAs and predicted target genes or transcriptional factors indicated that the dysregulated ileal lncRNAs were associated with lipid and amino acid metabolism-related pathways. Moreover, a series of lncRNAs and their potential target mRNAs, especially NONMMUT040618, , , and , were identified on the pathway. In conclusion DJB can induce remarkable alteration of ileal lncRNA and mRNA expression. The role of the ileum in DJB tends to re-establish the energy homeostasis by regulating the lipid and amino acid metabolism.

摘要

代谢与减重手术(MBS)可使胃肠道系统中编码和非编码RNA的表达模式发生剧烈变化,这会引发器官功能重塑,并可能促使2型糖尿病(T2D)缓解。我们之前的研究表明,十二指肠空肠旁路术(DJB,一种MBS的试验性手术和研究工具)后十二指肠和空肠长链非编码RNA(lncRNA)的表达谱发生改变,可分别通过调节肠 - 胰轴和肠 - 脑轴来改善血糖控制。作为肠道不可或缺的一部分,DJB术后回肠lncRNA的表达特征以及与受损代谢术后纠正相关的关键途径也需要进行研究。将高脂饮食诱导的糖尿病小鼠随机分为两组,分别接受DJB手术或假手术。与假手术组相比,DJB组中鉴定出1425个失调的回肠lncRNA和552个共表达的mRNA。对差异表达的mRNA以及预测的靶基因或转录因子进行生物信息学分析表明,失调的回肠lncRNA与脂质和氨基酸代谢相关途径有关。此外,在该途径上鉴定出了一系列lncRNA及其潜在的靶mRNA,尤其是NONMMUT040618等。总之,DJB可诱导回肠lncRNA和mRNA表达发生显著改变。回肠在DJB中的作用倾向于通过调节脂质和氨基酸代谢来重新建立能量稳态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e7cd/9021573/0436962204ed/fphys-13-836918-g001.jpg

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