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 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.Methods: CD4(+) T cells, CD8(+) T cells, and CD16(+) neutrophils were reiteratively isolated from blood, and 5mC levels were measured across >450,000 CG sites.Results: Nineteen CG sites were differentially methylated between women with obesity and with normal weight in CD4(+) cells, 16 CG sites in CD8(+) cells, and 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 4CG sites in CLSTN1's promoter, which, this study shows, may regulate its expression.Conclusions: 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.