Use of Blood as a Surrogate Model for the Assessment of Visceral AdiposeTissue Methylation Profiles Associated with the Metabolic Syndrome inMen

Epigenetic mechanisms are known to be involved in tissue-specific differentiation. DNA methylationpatterns have been shown to be largely conserved across tissues but with variation for specific genes. However, it is unclear whether the variability observed in the methylationprofile of a metabolically active tissue is reflected in other sources such as hematopoietic tissue. This study aimed to test blood genome-wide CpG site methylationlevels as a surrogate modelfor visceral adipose tissue (VAT) methylationand to verify whether it appropriately reflects differences in methylationlevels found in VAT between men discordant for the metabolic syndrome (MetS). Tissue specimens (VAT and blood samples) were obtained from 16 severely obeseindividuals discordant for the MetS. CpG sites methylationlevels were measured with the Infinium HumanMethylation450 BeadChip and correlations of methylationlevels between VAT and blood were computed. Differences in methylationlevels between individuals with and without MetS were tested in both tissues. Pathway analysiswas conducted for differentially methylated CpG sitescommon to both tissues. High cross-tissue correlations were observed for VAT and blood (0.952±0.014) while some CpG siteshad significantly different methylationlevels in VAT versus blood. Differential methylationanalysis between individuals with and without MetS demonstrated a higher number of differentially methylated CpG sitesin VAT than in blood (11,778 vs. 881, respectively) with nearly 4% of differentially methylatedsites found in VAT being also represented in blood. Common differentially methylatedsites were involved in inflammatory-, lipid- and diabetes-related pathways. These results suggest that blood methylationlevels of specific CpG sitesmay adequately reflect VAT methylationlevels for some of the MetS-related genes, specifically for inflammatory, lipid and glucose metabolism genes.