CD4+ AND CD8+ T CELL-SPECIFIC DNA CYTOSINE METHYLATION DIFFERENCES ASSOCIATED WITH OBESITY

OBJECTIVE: Lifestyle factors associated with obesity may alter epigenome-regulated gene expression. Most studies examining epigenetic changes in obesity analyze 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 we conducted a pilot study examining 5mC in three distinct leukocyte types isolated from peripheral blood of women of normal and obese weight. METHODS: CD4+ T cells, CD8+ T cells and CD16+ neutrophils were reiteratively isolated from blood and 5mC levels measured across >450,000 CG-sites. RESULTS: 19 CG-sites were differentially methylated between women of obese and normal weight in CD4+ cells, 16 CG-sites in CD8+ cells and zero CG-sites in CD16+ neutrophils (q<0.05). There were no common differentially methylated sites between the T cells types. The amount of visceral adipose tissue (VAT) was strongly associated with the methylation level of 79 CG-sites in CD4+ cells, including four CG-sites in CLSTN1’s promoter, which we show may regulate its expression. CONCLUSIONS: The methylomes of various leukocytes respond differently to obesity and levels of VAT. We identified highly significant differentially methylated sites in CD4+ and CD8+ cells in women of obese weight with apparent biological relevance to obesity.