4.7 Article

Blood Immune Cell Composition Associated with Obesity and Drug Repositioning Revealed by Epigenetic and Transcriptomic Conjoint Analysis

期刊

FRONTIERS IN PHARMACOLOGY
卷 12, 期 -, 页码 -

出版社

FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2021.714643

关键词

obesity; drug repositioning; epigenomics; transcriptomics; immunity; inflammation

资金

  1. Natural Science Foundation of Hunan Province [2020JJ5856]
  2. National undergraduate innovation training project [2020105330289]

向作者/读者索取更多资源

This research identified that CD8 + T cells and NK cells were significantly lower in obese individuals, and 11 drugs/compounds were considered to possess obesity-control potential. Furthermore, the expression of drug targets in obese patients were higher than those in controls, suggesting immune cells as potential therapeutic targets for obesity.
This research was designed to analyze the composition of immune cells in obesity and identify novel and potent drugs for obesity management by epigenetic and transcriptomic conjoint analysis. DNA methylation data set (GSE166611) and mRNA expression microarray (GSE18897) were obtained from the Gene Expression Omnibus database. A total of 72 objects (35 obese samples and 37 controls) were included in the study. Immune cell composition analysis, drug repositioning, and gene set enrichment analysis (GSEA) were performed using CIBERSORT, connectivity map (CMap), and GSEA tools. Besides, we performed a single-cell RNA-seq of the immune cells from whole blood samples obtained from one obese patient and one healthy control. mRNA levels of drug target genes were analyzed by qPCR assay in blood samples from six patients and six healthy controls. Immune cell composition analysis found that CD8 + T cells and NK cells were significantly lower in the obese group. 11 drugs/compounds are considered to possess obesity-control potential, such as atorvastatin. Moreover, the expression of drug targets (STAT3, MCL1, PMAIP1, SOD2, FOX O 3, FOS, FKBP5) in obese patients were higher than those in controls. In conclusion, immune cells are potential therapeutic targets for obesity. Our results also contribute to accelerate research on drug development of obesity.

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