Zhang Shao-Jun, Wang Yan, Yang Yan-Lan, Zheng Hong
Department of Endocrinology, The People's Hospital of Shanxi Province, Taiyuan, Shanxi 030012, China.
Department of Endocrinology, The Sixth Division Hospital of Xinjiang Production and Construction Corps, Wujiaqu, Xinjiang 830025, China.
Open Life Sci. 2018 Jun 2;13:201-207. doi: 10.1515/biol-2018-0024. eCollection 2018 Jan.
Epigenetics has been recognized as a significant regulator in many diseases. White adipose tissue (WAT) epigenetic dysregulation is associated with systemic insulin resistance (IR). The aim of this study was to survey the differential methylation of genes in obese women with systemic insulin resistance by DNA methylation microarray.
The genome-wide methylation profile of systemic insulin resistant obese women was obtained from Gene Expression Omnibus database. After data preprocessing, differing methylation patterns between insulin resistant and sensitive obese women were identified by Student's t-test and methylation value differences. Network analysis was then performed to reveal co-regulated genes of differentially methylated genes. Functional analysis was also implemented to reveal the underlying biological processes related to systemic insulin resistance in obese women.
Relative to insulin sensitive obese women, we initially screened 10,874 differentially methylated CpGs, including 7402 hyper-methylated sites and 6073 hypo-methylated CpGs. Our analysis identified 4 significantly differentially methylated genes, including , , , and . Network and functional analyses found that these differentially methylated genes were mainly involved in chondroitin and dermatan sulfate biosynthetic processes.
Based on our study, we propose several epigenetic biomarkers that may be related to obesity-associated insulin resistance. Our results provide new insights into the epigenetic regulation of disease etiology and also identify novel targets for insulin resistance treatment in obese women.
表观遗传学已被公认为多种疾病的重要调节因子。白色脂肪组织（WAT）的表观遗传失调与全身性胰岛素抵抗（IR）相关。本研究旨在通过DNA甲基化微阵列调查全身性胰岛素抵抗肥胖女性基因的差异甲基化情况。
从基因表达综合数据库获取全身性胰岛素抵抗肥胖女性的全基因组甲基化谱。经过数据预处理，通过学生t检验和甲基化值差异确定胰岛素抵抗和敏感肥胖女性之间不同的甲基化模式。然后进行网络分析以揭示差异甲基化基因的共同调控基因。还进行了功能分析以揭示肥胖女性中与全身性胰岛素抵抗相关的潜在生物学过程。
相对于胰岛素敏感肥胖女性，我们最初筛选出10874个差异甲基化的CpG，包括7402个高甲基化位点和6073个低甲基化的CpG。我们的分析确定了4个显著差异甲基化基因，包括 、 、 和 。网络和功能分析发现这些差异甲基化基因主要参与硫酸软骨素和硫酸皮肤素的生物合成过程。
基于我们的研究，我们提出了几种可能与肥胖相关胰岛素抵抗有关的表观遗传生物标志物。我们的结果为疾病病因的表观遗传调控提供了新见解，也为肥胖女性胰岛素抵抗治疗确定了新靶点。
