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

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.

Maternal Intake of n-3 Polyunsaturated Fatty Acids During Pregnancy Is Associated With Differential Methylation Profiles in Cord Blood White Cells

“…Furthermore, DNA methylation levels are specific to the type of cell and tissue (Bell et al, 2012). These methylation profiles in cord blood leukocytes might not represent DNA methylation in other tissues even though patterns are globally conserved (Ma et al, 2014; Ronn et al, 2015; Guénard et al, 2016). Finally, annotation of genetic variants has been deemed as inconsistent across databases, incomplete, and subjective toward known genes and pathway analysis that is statistically unpowered (Aslibekyan et al, 2014b).…”

Precision Nutrition: A Review of Personalized Nutritional Approaches for the Prevention and Management of Metabolic Syndrome

“…Recent studies have also suggested that whole genome differential methylation patterns derived from blood leukocytes (BL) may be used as surrogates of those derived from VAT. More specifically, a set of differentially methylated cytosine-phosphate-guanine (CpG) sites, common in VAT and BL, were shown to successfully discriminate men with or without metabolic syndrome [ 100 ]. These and other results suggest that BL methylation levels could be a good marker of VAT DNA methylation [ 101 ], and could then be used to determine the effect of a nutritional intervention on the epigenetic profile, and therefore on metabolic health related to VAT accumulation.…”

Body mass index is associated with epigenetic age acceleration in the visceral adipose tissue of subjects with severe obesity

“…Focusing on epigenetics, we and others have shown that altered DNA methylation in obesity would be associated to increased prevalence of metabolic comorbidities [8–13]. As such, both global methylation differences observed in blood and tissue-specific methylation alterations have been found to be associated with healthy or unhealthy obesity phenotypes [14, 15]. Likewise, given the innate plasticity of DNA methylation at cytosine-phosphate-guanine (CpG) dinucleotides [16], its modulation appears to be mediated through numerous environmental and lifestyle factors, such as diet or metabolic stress, as well as by intrinsic individual features, mainly sex and age [17].…”