OR51-1 METHYLATION PROFILE OF SUBCUTANEOUS AND VISCERAL ADIPOSE TISSUE IN LEAN AND OBESE SUBJECTS

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR51-Obesity: From Genes to Populations
Translational
Tuesday, June 18, 2013: 9:15 AM-10:45 AM
Presentation Start Time: 9:15 AM
Room 303 (Moscone Center)
Anna Maria Di Blasio*1, Raffaella Cancello1, Davide Gentilini1, Alessandra Zulian2, Giancarlo Micheletto3, Sabrina Maestrini1, Monica Mencarelli1 and Cecilia Invitti4
1Istituto Auxologico Italiano, Cusano Milanino, Italy, 2Istituto Auxologico Italiano, Milano, Italy, 3University of Milano, Milano, Italy, 4Istituto Auxologico Italiano, Milano, Italy
Differences between visceral (VAT) and subcutaneous (SAT) adipose tissue arise from precursor cells and tissue micro-environment. Compared with SAT, VAT is more hyperplasic and less hypertrophic, enriched of vascular endothelial cells and, especially in obesity, contains a larger number of inflammatory and immune cells. Recently, autologous transplantation of VAT to SAT suggested that  DNA methylation of adipose specific gene promoters is depot-specific and is influenced by local factors. Epigenetic regulation of SAT/VAT regional differences has not been evaluated in humans. Thus, the aim of this study was to investigate the association between DNA methylation of SAT/VAT adipose depots and obesity-related phenotypes in a cohort of healthy normal weight and obese subjects. 28 subjects were enrolled: 9 were normal weight (NW, mean age: 42.2±10.6 years, mean BMI: 23.8±1.8 Kg/m2) and 19 were obese (OB, mean age: 41.6±9.2 years, mean BMI: 40.5±4.2 Kg/m2). Paired biopsies of SAT and VAT were obtained from all the NW subjects and from 10 OB patients while only SAT was available in the remaining 9 OB. Genomic DNA was extracted from each sample and analyzed with the Infinium Human Methylation 450 Bead Chip after bisulphite conversion. This system allows to simultaneously analyze more than 450,000 sites of methylation with a high resolution. Anthropometric and bio-clinical data of each enrolled patient were recorded in a database to perform association studies. A significant hyper-methylation of VAT compared to SAT was observed (72% vs. 69%, p=0.002) independently of BMI. This difference was still significant in the OB sub-group (p=0.003). A significant association was found between SAT global methylation levels and metabolic parameters when considering all the subjects, while VAT global methylation levels was associated to inflammatory markers only in the OB group. The delta beta analysis led us to identify SAT and VAT hyper- and hypo-methylated genes. To the best of our knowledge, this is the first surveys of the methylation profile of human SAT and VAT. The results indicate that intrinsic methylation differences between SAT and VAT are dependent on their localization rather than BMI. Additionally, they also show that VAT global methylation levels are associated with immune response parameters in human obesity. These observations open new insights for future identification of epigenetic biomarkers to predict/prevent obesity and obesity comorbidities risks.

Nothing to Disclose: AMD, RC, DG, AZ, GM, SM, MM, CI

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

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