1. CD4 + and CD8 + T-Cell-Specific DNA Cytosine Methylation Differences Associated With Obesity.
- Author
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Hohos NM, Smith AK, Kilaru V, Park HJ, Hausman DB, Bailey LB, Lewis RD, Phillips BG, and Meagher RB
- Subjects
- Adolescent, Adult, Case-Control Studies, Cells, Cultured, Cytosine, Epigenesis, Genetic physiology, Female, Gene Expression Regulation, Humans, Ideal Body Weight genetics, Intra-Abdominal Fat metabolism, Leukocytes metabolism, Obesity metabolism, Pilot Projects, Promoter Regions, Genetic, Young Adult, CD4-Positive T-Lymphocytes metabolism, CD8-Positive T-Lymphocytes metabolism, DNA Methylation physiology, Obesity genetics, Obesity immunology
- Abstract
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 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., 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., (© 2018 The Obesity Society.)- Published
- 2018
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