Abstract
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.
Highlights
Obesity is a chronic metabolic disease caused by the interaction of genetic, environmental, and other factors
Analysis of the methylation profiles by the EpiDISH algorithm was used to estimate the proportion of obesity-related immune cell composition
The results showed the low-density lipoprotein particle remodeling, positive regulation of calcium ion import, and cyclic nucleotide phosphodiesterase activity genes were significantly enriched in the obesity groups (Figure 1B)
Summary
Obesity is a chronic metabolic disease caused by the interaction of genetic, environmental, and other factors. Recent data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES) suggest the age-adjusted prevalence of obesity among United States adults was 42.4% and exerted an increasing trend year by year (Fryar and Afful, 2020a; Fryar and Afful, 2020b). As a leading mortality risk factor for Type 2 Diabetes (T2D), coronary heart disease, and other chronic diseases, obesity imposes a considerable economic burden on our medical system and the whole society. A meta-analysis of 97 studies, including 1.8 million participants, suggested that obesity has been linked to an increased risk of coronary heart disease and stroke. There is an urgent need to address the substantial social burden caused by obesity
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