Open Access Research

LINE-1 methylation in visceral adipose tissue of severely obese individuals is associated with metabolic syndrome status and related phenotypes

Valérie Turcot13, André Tchernof24, Yves Deshaies45, Louis Pérusse16, Alexandre Bélisle7, Simon Marceau48, Simon Biron48, Odette Lescelleur48, Laurent Biertho48 and Marie-Claude Vohl13*

Author Affiliations

1 Institute of Nutraceuticals and Functional Foods, 2440 Hochelaga Blvd, Québec City, G1V 0A6, Canada

2 Molecular Endocrinology and Genomics, CHUL Research Center, 2705 Laurier Blvd, Québec City, G1V 4G2, Canada

3 Department of Food Sciences and Nutrition, Université Laval, 2425 de l’Agriculture Av, Québec City, G1V 0A6, Canada

4 Centre de Recherche de l’Institut Universitaire de Cardiologie et de Pneumologie de Québec, 2725 Sainte-Foy Rd, Québec City, G1V 4G5, Canada

5 Department of Medicine, Université Laval, 1050 de la Médecine Av, Québec City, G1V 0A6, Canada

6 Department of Kinesiology, Université Laval, 2300 de la Terrasse Street, Québec City, G1V 0A6, Canada

7 Genotyping Platform Team, McGill University and Génome Québec Innovation Center, 740 Docteur-Penfield Av, Montréal, H3A 1A4, Canada

8 Department of Surgery, Université Laval, 1050 de la Médecine Av, Québec City, G1V 0A6, Canada

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Clinical Epigenetics 2012, 4:10  doi:10.1186/1868-7083-4-10

Published: 2 July 2012

Abstract

Background

Epigenetic mechanisms may be involved in the regulation of genes found to be differentially expressed in the visceral adipose tissue (VAT) of severely obese subjects with (MetS+) versus without (MetS-) metabolic syndrome (MetS). Long interspersed nuclear element 1 (LINE-1) elements DNA methylation levels (%meth) in blood, a marker of global DNA methylation, have recently been associated with fasting glucose, blood lipids, heart diseases and stroke.

Aim

To test whether LINE-1%meth levels in VAT are associated with MetS phenotypes and whether they can predict MetS risk in severely obese individuals.

Methods

DNA was extracted from VAT of 34 men (MetS-: n = 14, MetS+: n = 20) and 152 premenopausal women (MetS-: n = 84; MetS+: n = 68) undergoing biliopancreatic diversion for the treatment of obesity. LINE-1%meth levels were assessed by pyrosequencing of sodium bisulfite-treated DNA.

Results

The mean LINE-1%meth in VAT was of 75.8% (SD = 3.0%). Multiple linear regression analyses revealed that LINE-1%meth was negatively associated with fasting glucose levels (β = -0.04; P = 0.03), diastolic blood pressure (β =  -0.65; P = 0.03) and MetS status (β = -0.04; P = 0.004) after adjustments for the effects of age, sex, waist circumference (except for MetS status) and smoking. While dividing subjects into quartiles based on their LINE-1%meth (Q1 to Q4: lower %meth to higher %meth levels), greater risk were observed in the first (Q1: odds ratio (OR) = 4.37, P = 0.004) and the second (Q2: OR = 4.76, P = 0.002) quartiles compared to Q4 (1.00) when adjusting for age, sex and smoking.

Conclusions

These results suggest that lower global DNA methylation, assessed by LINE-1 repetitive elements methylation analysis, would be associated with a greater risk for MetS in the presence of obesity.

Keywords:
Blood pressure; Epigenetics; Fasting glucose; Global DNA methylation; LINE-1; Metabolic syndrome; Severe obesity; Visceral adipose tissue