Identification of Key Genes from the Visceral Adipose Tissues of Overweight/Obese Adults with Hypertension through Transcriptome Sequencing

Abstract

Overweight and obese (OW/OB) adults are at increased risk of hypertension due to visceral adipose tissue (VAT) inflammation. In this study, we explored gene level differences in the VAT of hypertensive and normotensive OW/OB patients. VAT samples obtained from six OW/OB adults (three hypertensive, three normotensive) were subjected to transcriptome sequencing analysis. Gene set enrichment analysis was conducted for all gene expression data to identify differentially expressed genes (DEGs) with |log2 (fold change)| ≥ 1 and q < 0.05. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses were performed on the DEGs and hub genes were identified by constructing a protein-protein interaction (PPI) network. The proposed hub genes were validated using quantitative real-time PCR in ten other samples from five hypertensive and five normotensive patients. In addition, we performed ROC analysis and spearman correlation analysis. A total of 84 DEGs were identified between VAT samples from OW/OB patients with and without hypertension, among which 21 were significantly up-regulated and 63 were significantly down-regulated. Bioinformatics analysis revealed that spleen function was related to hypertension in OW/OB adults. Meanwhile, PPI network analysis identified the following top 10 hub genes: CD79A, CR2, SELL, CD22, IL7R, CCR7, TNFRSF13C, CXCR4, POU2AF1, and JAK3. Through qPCR verification, we found that CXCR4, CD22 and IL7R were statistically significant. QPCR verification suggested that RELA were statistically significant. However, qPCR verification indicated that NF-KB1 and KLF2 were not statistically significant. These hub genes were mainly regulated by the transcription factors RELA. The AUC of ROC analysis for CXCR4, IL7R and CD22 was 0.92. What’s more, VAT CXCR4 and CD22 were positively related to RELA relative expression levels. Take together, our research demonstrates that CXCR4, IL7R and CD22 related to VAT in hypertensive OW/OB adults could serve as future therapeutic targets.

Whole genome sequencing of mouse lines divergently selected for fatness (FLI) and leanness (FHI) revealed several genetic variants as candidates for novel obesity genes

“…These results make Cx3cr and its polymorphisms in the Fat line strong obesity candidates. Meanwhile, CD22 (CD22 antigen) was suggested as potential therapeutic target in hypertensive overweight and obese adults (Liao et al 2022 ).…”

B-cell hub genes play a cardiovascular pathogenic role of in childhood obesity and Kawasaki disease as revealed by transcriptomics-based analyses

“…CD79A, expressed in B-cell and plasma cell precursors, is a potential candidate for inducing apoptosis and inhibiting B-cell receptor (BCR) activation, which could be relevant to eliminating ectopic germinal centers 43 . In overweight and obese (OW/OB) adults, VAT inflammation and CD79A have been implicated in the development of hypertension 44 . MZB1, a B cell-specific protein that is located in the endoplasmic reticulum, is connected to inflammation and is implicated in a number of inflammatory disorders, including chronic periodontal conditions and several malignancies 45 .…”