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基于生物信息学方法鉴定高脂肪饮食诱导肥胖内脏脂肪组织中的主要枢纽基因。

Identification of major hub genes involved in high-fat diet-induced obese visceral adipose tissue based on bioinformatics approach.

机构信息

Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, P. R. China.

Department of Cardiology, Zhejiang Provincial People's Hospital, Hangzhou, P. R. China.

出版信息

Adipocyte. 2023 Dec;12(1):2169227. doi: 10.1080/21623945.2023.2169227.

Abstract

High-fat diet (HFD) can cause obesity, inducing dysregulation of the visceral adipose tissue (VAT). This study aimed to explore potential biological pathways and hub genes involved in obese VAT, and for that, bioinformatic analysis of multiple datasets was performed. The expression profiles (GSE30247, GSE167311 and GSE79434) were downloaded from Gene Expression Omnibus. Overlapping differentially expressed genes (ODEGs) between normal diet and HFD groups in GSE30247 and GSE167311 were selected to run protein-protein interaction network, GO and KEGG analysis. The hub genes in ODEGs were screened by Cytoscape software and further verified in GSE79434 and obese mouse model. A total of 747 ODEGs (599 up-regulated and 148 down-regulated) were screened, and the GO and KEGG analysis showed that the up-regulated ODEGs were significantly enriched in inflammatory response and extracellular matrix receptor interaction pathways. On the other hand, the down-regulated ODEGs were involved in metabolic pathways; however, there were no significant KEGG pathways. Furthermore, six hub genes, Mki67, Rac2, Itgb2, Emr1, Tyrobp and Csf1r were acquired. These pathways and genes were verified in GSE79434 and VAT of obese mice. This study revealed that HFD induced VAT expansion, inflammation and fibrosis, and the hub genes could be used as therapeutic biomarkers in obesity.

摘要

高脂肪饮食(HFD)可导致肥胖,引起内脏脂肪组织(VAT)失调。本研究旨在探索肥胖 VAT 中涉及的潜在生物学途径和枢纽基因,为此对多个数据集进行了生物信息学分析。从基因表达综合数据库(Gene Expression Omnibus)下载了表达谱(GSE30247、GSE167311 和 GSE79434)。从 GSE30247 和 GSE167311 中选择正常饮食组和 HFD 组之间的差异表达基因(DEGs)重叠部分进行蛋白质-蛋白质互作网络、GO 和 KEGG 分析。使用 Cytoscape 软件筛选 DEGs 中的枢纽基因,并在 GSE79434 和肥胖小鼠模型中进一步验证。共筛选出 747 个 DEGs(599 个上调和 148 个下调),GO 和 KEGG 分析表明,上调的 DEGs 在炎症反应和细胞外基质受体相互作用途径中显著富集。另一方面,下调的 DEGs 参与代谢途径,但没有显著的 KEGG 途径。此外,还获得了 6 个枢纽基因,包括 Mki67、Rac2、Itgb2、Emr1、Tyrobp 和 Csf1r。这些途径和基因在 GSE79434 和肥胖小鼠的 VAT 中得到了验证。本研究表明,HFD 诱导 VAT 扩张、炎症和纤维化,枢纽基因可作为肥胖症的治疗生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/271f/9897782/d232260cc8f4/KADI_A_2169227_F0001_B.jpg

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