CD4+ and CD8+ T-Cell-Specific DNA Cytosine Methylation Differences Associated With Obesity.

Abstract

ObjectiveLifestyle 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.MethodsCD4+ T cells, CD8+ T cells and CD16+ neutrophils were reiteratively isolated from blood and 5mC levels measured across >450,000 CG-sites.Results19 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.ConclusionsThe 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.