DNA Methylation Profiles of Blood Cells Are Distinct between Early-Onset Obese and Control Individuals

Abstract

Obesity is a highly prevalent, chronic disorder that has been increasing in incidence in young patients. Both epigenetic and genetic aberrations may play a role in the pathogenesis of obesity. Therefore, in-depth epigenomic and genomic analyses will advance our understanding of the detailed molecular mechanisms underlying obesity and aid in the selection of potential biomarkers for obesity in youth. Here, we performed microarray-based DNA methylation and gene expression profiling of peripheral white blood cells obtained from six young, obese individuals and six healthy controls. We observed that the hierarchical clustering of DNA methylation, but not gene expression, clearly segregates the obese individuals from the controls, suggesting that the metabolic disturbance that occurs as a result of obesity at a young age may affect the DNA methylation of peripheral blood cells without accompanying transcriptional changes. To examine the genome-wide differences in the DNA methylation profiles of young obese and control individuals, we identified differentially methylated CpG sites and investigated their genomic and epigenomic contexts. The aberrant DNA methylation patterns in obese individuals can be summarized as relative gains and losses of DNA methylation in gene promoters and gene bodies, respectively. We also observed that the CpG islands of obese individuals are more susceptible to DNA methylation compared to controls. Our pilot study suggests that the genome-wide aberrant DNA methylation patterns of obese individuals may advance not only our understanding of the epigenomic pathogenesis but also early screening of obesity in youth.

DNA methylation markers in obesity, metabolic syndrome, and weight loss

“…For example, the offspring of obese mothers presented several CpG sites differentially methylated in cord blood in comparison with offspring from normal weight mothers [87]. Other regions studied, were mainly hypomethylated in obese children and located in the gene body region, and revealed a unique cluster of obese individuals that was differentiated from the normal weight children [88]. In addition, some of these genes are implicated in lipid and glucose metabolism, differential body size and body composition in children [89].…”

Nutritional Factors, DNA Methylation, and Risk of Type 2 Diabetes and Obesity: Perspectives and Challenges

“…In this regard, epigenetic dysregulation of several genes ( Nna t and Peg3 ) of the Trim28 -imprinted gene network also influences the risk for the offspring of developing obesity, as elegantly described by Dalgaard et al [79]. Additionally, the DNA methylation signature in blood cells is distinct between early-onset obese and control individuals [80]. Moreover, Dick et al [81] described an association between an increased BMI and an increased methylation at the HIF3A locus in blood cells and in adipose tissue of the same subjects, suggesting that DNA methylation perturbation of hypoxia-inducible factor (HIF) signaling might represent a mark of increased body adiposity.…”

Epigenetic approach in obesity: DNA methylation in a prepubertal population which underwent a lifestyle modification

“…Some cross-sectional studies have reported a significant association between obesity or adiposity status, and DNA methylation [ 24 ]. These studies demonstrate that some regions of different genes studied were hypomethylated in obese children and located in the gene body region, and revealed a unique cluster of obese individuals that was differentiated from the normal-weight children [ 25 ]. Some of these genes are implicated in lipid and glucose metabolism, differential body size, and body composition in children [ 26 ].…”