Liu Jia-Chen, Liu Sheng-Hua, Fu Guang, Qiu Xiao-Rui, Jiang Run-Dong, Huang Sheng-Yuan, Zhu Li-Yong, Li Wei-Zheng
Center of Biomedical Informatics and Genomics, Xiangya Medical College of Central South University, Changsha, China.
Department of Gastroenterology, The First Affiliated Hospital of University of South, Hengyang, China.
Front Pharmacol. 2021 Oct 12;12:714643. doi: 10.3389/fphar.2021.714643. eCollection 2021.
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 () 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.
本研究旨在通过表观遗传学和转录组联合分析，剖析肥胖症中免疫细胞的组成，并识别用于肥胖症管理的新型强效药物。DNA甲基化数据集（GSE166611）和mRNA表达微阵列（GSE18897）取自基因表达综合数据库。该研究共纳入72个对象（35个肥胖样本和37个对照）。使用CIBERSORT、连通性图谱（CMap）和基因集富集分析（GSEA）工具进行免疫细胞组成分析、药物重新定位和基因集富集分析。此外，我们对一名肥胖患者和一名健康对照的全血样本中的免疫细胞进行了单细胞RNA测序。通过qPCR检测分析了6名患者和6名健康对照血液样本中药物靶基因的mRNA水平。免疫细胞组成分析发现，肥胖组中CD8 + T细胞和NK细胞显著减少。11种药物/化合物被认为具有控制肥胖的潜力，如阿托伐他汀。此外，肥胖患者中药物靶点（）的表达高于对照组。总之，免疫细胞是肥胖症潜在的治疗靶点。我们的研究结果也有助于加快肥胖症药物开发的研究。
