Use of Blood as a Surrogate Model for the Assessment of Visceral Adipose Tissue Methylation Profiles Associated with the Metabolic Syndrome in Men

Frédéric Guénard,Yves Deshaies

doi:10.4172/1747-0862.1000198

Abstract

Epigenetic mechanisms are known to be involved in tissue-specific differentiation. DNA methylation patterns 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 methylation profile of a metabolically active tissue is reflected in other sources such as hematopoietic tissue. This study aimed to test blood genome-wide CpG site methylation levels as a surrogate model for visceral adipose tissue (VAT) methylation and to verify whether it appropriately reflects differences in methylation levels found in VAT between men discordant for the metabolic syndrome (MetS). Tissue specimens (VAT and blood samples) were obtained from 16 severely obese individuals discordant for the MetS. CpG sites methylation levels were measured with the Infinium HumanMethylation450 BeadChip and correlations of methylation levels between VAT and blood were computed. Differences in methylation levels between individuals with and without MetS were tested in both tissues. Pathway analysis was conducted for differentially methylated CpG sites common to both tissues. High cross-tissue correlations were observed for VAT and blood (0.952±0.014) while some CpG sites had significantly different methylation levels in VAT versus blood. Differential methylation analysis between individuals with and without MetS demonstrated a higher number of differentially methylated CpG sites in VAT than in blood (11,778 vs. 881, respectively) with nearly 4% of differentially methylated sites found in VAT being also represented in blood. Common differentially methylated sites were involved in inflammatory-, lipid- and diabetes-related pathways. These results suggest that blood methylation levels of specific CpG sites may adequately reflect VAT methylation levels for some of the MetS-related genes, specifically for inflammatory, lipid and glucose metabolism genes.

Highlights

The metabolic syndrome (MetS) is defined as the clustering of abdominal obesity, impaired glucose tolerance, dyslipidemia, and hypertension [1] increasing the risk of chronic diseases which represent major causes of death worldwide [2]
Guénard F, Deshaies Y, Hould FS, Lebel S, Tchernof A, et al (2016) Use of Blood as a Surrogate Model for the Assessment of Visceral Adipose Tissue Methylation Profiles Associated with the Metabolic Syndrome in Men
These results are consistent with those previously published in studies evaluating blood and other tissues either focusing on CpG island or genome-wide methylation levels [20,21,26,33,34,35], which demonstrated that DNA methylation patterns are globally conserved across tissues

Summary

Introduction

The metabolic syndrome (MetS) is defined as the clustering of abdominal obesity, impaired glucose tolerance, dyslipidemia, and hypertension [1] increasing the risk of chronic diseases which represent major causes of death worldwide [2]. MetS appears as a polygenic condition affected by environmental factors [3]. Considering that gene expression is affected by both genetic and environmental factors [7,8], evaluation of these two etiological components is needed to get a better understanding of MetS. Epigenetic marks are involved in the acquisition and maintenance of organized tissues [10,11]. Being altered by both genetic and environmental factors, it represents a potential link through which genetics and environment may cause phenotypic variation [12] and may provide a molecular basis for the theory of developmental origin of health and

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Methods

Conclusion