Wu Peili, Guo Lei, Li Xuelin, Du Yuejun, Lin Xiaochun, Ma Xiaoqin, Lin Yingbei, Wen Churan, Yang Chuyi, Liu Nannan, Feng Qijian, Xue Yaoming, Guan Meiping
Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Department of Urology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
Front Genet. 2022 Oct 14;13:1024300. doi: 10.3389/fgene.2022.1024300. eCollection 2022.
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, , , , , , , and . 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.
DNA甲基化与许多疾病的发生和发展密切相关,但其在肥胖症中的作用仍不清楚。本研究旨在寻找与肥胖症发生和发展相关的潜在差异甲基化基因。通过结合甲基化和转录组分析,我们确定了脂肪组织中影响肥胖症发生和发展的关键基因,并揭示了肥胖症发病机制中可能涉及的分子机制。我们首先筛选了14个甲基化相关差异基因,并通过定量聚合酶链反应(qPCR)验证了它们在脂肪组织中的表达。七个具有相同表达模式的基因被确定为关键基因,即 , , , , , ,和 。然后,通过CIBERSORT对脂肪组织的免疫微环境进行定量分析,我们发现肥胖组脂肪组织中M0巨噬细胞和滤泡辅助性T细胞的含量分别显著增加和减少。此外,分析了关键基因与免疫微环境之间的关系。另外,基于ssGSEA算法计算每个样本的代谢途径活性,并构建关键基因-代谢网络。此外,我们基于脂肪组织中的差异基因进行了CMAP分析,以筛选出可能对肥胖症治疗有效的药物。总之,我们确定了七个与肥胖症发病机制密切相关的甲基化相关关键基因,并探索了它们在肥胖症中发挥作用的潜在机制。本研究为肥胖症的分子机制和管理提供了新的见解。