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通过生物信息学分析获得减重手术后皮下脂肪组织中受调控的关键基因。

Bioinformatics analysis to obtain critical genes regulated in subcutaneous adipose tissue after bariatric surgery.

机构信息

Center of Gastrointestinal Disease, The Affiliated Changzhou NO. 2 People's Hospital of Nanjing Medical University, Changzhou, China.

出版信息

Adipocyte. 2022 Dec;11(1):550-561. doi: 10.1080/21623945.2022.2115212.

Abstract

Bariatric surgery (BS) is a dependable method for managing obesity and metabolic diseases, however, the regulatory processes of lipid metabolism are still not well elucidated. Differentially expressed genes (DEGs) were analysed through three transcriptomic datasets of GSE29409, GSE59034 and GSE72158 from the GEO database regarding subcutaneous adipose tissue (SAT) after BS, and 37 DEGs were identified. The weighted gene co-expression network analysis (WGCNA), last absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms further screened four key genes involved in the regulation of STMN2, SFRP4, APOE and MXRA5. The GSE53376 dataset was used to further confirm the differential expression of SFRP4, APOE and MXRA5 in the postoperative period. GSEA analysis reveals activation of immune-related regulatory pathways after surgery. Finally, the silencing of MXRA5 was found by experimental methods to affect the expression of PPARγ and CEBPα during the differentiation of preadipocytes, as well as to affect the formation of lipid droplets. In conclusion, SAT immunoregulation was mobilized after BS, while MXRA5 was involved in the regulation of lipid metabolism.

摘要

减重手术(BS)是一种可靠的肥胖和代谢性疾病治疗方法,然而,脂质代谢的调控机制仍未完全阐明。本研究通过分析 GEO 数据库中三个关于 BS 后皮下脂肪组织(SAT)的转录组数据集 GSE29409、GSE59034 和 GSE72158,共鉴定出 37 个差异表达基因(DEGs)。加权基因共表达网络分析(WGCNA)、最小绝对值收缩和选择算子(LASSO)逻辑回归和支持向量机递归特征消除(SVM-RFE)算法进一步筛选出 STMN2、SFRP4、APOE 和 MXRA5 四个关键基因,参与 SAT 免疫调节。GSE53376 数据集进一步证实了 SFRP4、APOE 和 MXRA5 在术后的差异表达。GSEA 分析显示,手术后免疫相关调控途径被激活。最后,实验方法发现沉默 MXRA5 会影响前脂肪细胞分化过程中 PPARγ 和 CEBPα 的表达,并影响脂质滴的形成。综上所述,BS 后 SAT 免疫调节被激活,而 MXRA5 参与了脂质代谢的调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2da6/9427031/b245b730f84a/KADI_A_2115212_F0003_OC.jpg

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