Comprehensive analysis of epigenomics and transcriptome data to identify potential target genes associated with obesity

Abstract

DNA methylation is closely related to the occurrence and development of many diseases, but its role in obesity is still unclear. This study aimed to find the potential differentially methylated genes associated with obesity occurrence and development. By combining methylation and transcriptome analysis, we identified the key genes in adipose tissue affecting the occurrence and development of obesity and revealed the possible molecular mechanisms involved in obesity pathogenesis. We first screened 14 methylation-related differential genes and verified their expression in adipose tissue by quantitative polymerase chain reaction (qPCR). Seven genes with the same expression pattern were identified as key genes, namely, CCRL2, GPT, LGALS12, PC, SLC27A2, SLC4A4, and TTC36. Then, the immune microenvironment of adipose tissue was quantified by CIBERSORT, and we found that the content of M0 macrophages and T follicular helper cells in adipose tissue was significantly increased and decreased, respectively, in the obese group. Furthermore, the relationship between key genes and the immune microenvironment was analyzed. Additionally, the metabolic pathway activity of each sample was calculated based on the ssGSEA algorithm, and the key gene–metabolic network was constructed. Moreover, we performed a CMAP analysis based on the differential genes in adipose tissue to screen out drugs potentially effective in obesity treatment. In conclusion, we identified seven methylation-related key genes closely related to obesity pathogenesis and explored the potential mechanism of their role in obesity. This study provided novel insights into the molecular mechanisms and management of obesity.

A genome-wide cross-trait analysis identifies shared loci and causal relationships of obesity and lipidemic traits with psoriasis

“…Among the 2 shared SNPs between LDL and psoriasis, rs28484982 was near RGS12, a gene that exhibited differential expression in visceral adipose tissue from morbidly obese patients ( 38 ). Among the 5 TG-psoriasis shared SNPs, rs140430387 was near TTC36, a gene identified as a key player in obesity ( 39 ). Notably, among the apoA1-proriasis and TC-psoriasis shared SNPs, none of them were found to be associated with dyslipidemia or obesity.…”

“…UBE2E2, a gene associated with obesity and type 2 diabetes, encodes the ubiquitin-conjugating enzyme E2E2 expressed in adipose tissue, and it plays a regulatory role in insulin synthesis and secretion as well as adipocyte differentiation ( 37 , 57 – 60 ). RGS12, which was differentially expressed in visceral adipose tissue from morbidly obese patients, and TTC36, which is involved in the occurrence and development of obesity, likely through the immune microenvironment, have both garnered recent attention ( 38 , 39 ). In terms of lipid traits, we did not observe any significant genetic correlations with psoriasis.…”

Network Pharmacology‐Based Identification of Key Targets of Ziyin Mingmu Pills Acting on Age‐Related Macular Degeneration

“…CIBERSORT is an analytical tool to provide an estimation of the abundances of member cell types in a mixed cell population using gene expression data [ 15 ]. The RNA-seq data on patients with AMD were analyzed by CIBERSORT to reveal the relative proportions of 22 immune-infiltrating cells and perform the spearman correlation analysis of gene expression and immune cell content.…”

M6A modification and T cells in adipose tissue inflammation

“…67 Some studies have shown that T FH cells are less abundant in adipose tissue, but the regulators of T FH cells are widely present in adipose tissue. 68,69 The role of m6A and METTL3 in the differentiation and activation of T FH cells has been studied relatively abundantly. In CD4 + T cells, the deficiency of METTL3 impairs the stability of m6A-modified Transcription factor 7 (Tcf7) mRNA, leading to impaired activation of the T FH transcriptional program and affecting its differentiation.…”

“…Promotes germinal center (GC) formation, antibody affinity maturation, and memory B cell generation 67 . Some studies have shown that T FH cells are less abundant in adipose tissue, but the regulators of T FH cells are widely present in adipose tissue 68,69 . The role of m6A and METTL3 in the differentiation and activation of T FH cells has been studied relatively abundantly.…”