Department of Foods and Nutrition, University of Georgia, Athens, Georgia, USA.
Psychiatry and Behavioral Sciences, University of Emory School of Medicine, Atlanta, Georgia, USA.
Obesity (Silver Spring). 2018 Aug;26(8):1312-1321. doi: 10.1002/oby.22225. Epub 2018 Jun 28.
Lifestyle factors associated with obesity may alter epigenome-regulated gene expression. Most studies examining epigenetic changes in obesity have analyzed DNA 5´-methylcytosine (5mC) in whole blood, representing a weighted average of several distantly related and regulated leukocyte classes. To examine leukocyte-specific differences associated with obesity, a pilot study examining 5mC in three distinct leukocyte types isolated from peripheral blood of women with normal weight and obesity was conducted.
CD4 T cells, CD8 T cells, and CD16 neutrophils were reiteratively isolated from blood, and 5mC levels were measured across >450,000 CG sites.
Nineteen CG sites were differentially methylated between women with obesity and with normal weight in CD4 cells, 16 CG sites in CD8 cells, and 0 CG sites in CD16 neutrophils (q < 0.05). There were no common differentially methylated sites between the T-cell types. The amount of visceral adipose tissue was strongly associated with the methylation level of 79 CG sites in CD4 cells, including 4 CG sites in CLSTN1's promoter, which, this study shows, may regulate its expression.
The methylomes of various leukocytes respond differently to obesity and levels of visceral adipose tissue. Highly significant differentially methylated sites in CD4 and CD8 cells in women with obesity that have apparent biological relevance to obesity were identified.
与肥胖相关的生活方式因素可能会改变受表观基因组调控的基因表达。大多数研究肥胖相关的表观遗传变化的研究都分析了全血中的 DNA 5´-甲基胞嘧啶（5mC），这代表了几种远距离相关和受调节的白细胞类别的加权平均值。为了研究与肥胖相关的白细胞特异性差异，进行了一项试点研究，该研究检查了来自正常体重和肥胖女性外周血的三种不同白细胞类型中的 5mC。
从血液中反复分离 CD4 T 细胞、CD8 T 细胞和 CD16 中性粒细胞，并在超过 450,000 个 CG 位点上测量 5mC 水平。
在 CD4 细胞中，肥胖女性与正常体重女性之间有 19 个 CG 位点存在差异甲基化，在 CD8 细胞中有 16 个 CG 位点，在 CD16 中性粒细胞中则没有差异甲基化 CG 位点（q<0.05）。T 细胞类型之间没有共同的差异甲基化位点。内脏脂肪组织的含量与 CD4 细胞中 79 个 CG 位点的甲基化水平强烈相关，其中包括 CLSTN1 启动子中的 4 个 CG 位点，本研究表明这些 CG 位点可能调节其表达。
各种白细胞的甲基组对肥胖和内脏脂肪组织水平的反应不同。在肥胖女性的 CD4 和 CD8 细胞中发现了高度显著的差异甲基化位点，这些位点与肥胖有明显的生物学相关性。
