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Title: Genome-wide DNA methylation pattern in visceral adipose tissue differentiates insulin-resistant from insulin-sensitive obese subject
Author: Crujeiras, Ana B.
Diaz-Lagares, Angel
Moreno-Navarrete, J. M.
Sandoval, Juan
Hervas, David
Gomez, A.
Ricart Engel, Wifredo
Casanueva, Felipe F.
Esteller, Manel
Fernandez-Real, J. M.
Keywords: ADN
Teixit adipós
Resistència a la insulina
Diabetis no-insulinodependent
Obesitat mòrbida
Adipose tissues
Insulin resistance
Non-insulin-dependent diabetes
Morbid obesity
Issue Date: 14-Jul-2016
Publisher: Elsevier
Abstract: Elucidating the potential mechanisms involved in the detrimental effect of excess body weight on insulin action is an important priority in counteracting obesity-associated diseases. The present study aimed to disentangle the epigenetic basis of insulin resistance by performing a genome-wide epigenetic analysis in visceral adipose tissue (VAT) from morbidly obese patients depending on the insulin sensitivity evaluated by the clamp technique. The global human methylome screening performed in VAT from 7 insulin-resistant (IR) and 5 insulin-sensitive (IS) morbidly obese patients (discovery cohort) analyzed using the Infinium HumanMethylation450 BeadChip array identified 982 CpG sites able to perfectly separate the IR and IS samples. The identified sites represented 538 unique genes, 10% of which were diabetes-associated genes. The current work identified novel IR-related genes epigenetically regulated in VAT, such as COL9A1, COL11A2, CD44, MUC4, ADAM2, IGF2BP1, GATA4, TET1, ZNF714, ADCY9, TBX5, and HDACM. The gene with the largest methylation fold-change and mapped by 5 differentially methylated CpG sites located in island/shore and promoter region was ZNF714. This gene presented lower methylation levels in IR than in IS patients in association with increased transcription levels, as further reflected in a validation cohort (n = 24; 11 IR and 13 IS). This study reveals, for the first time, a potential epigenetic regulation involved in the dysregulation of VAT that could predispose patients to insulin resistance and future type 2 diabetes in morbid obesity, providing a potential therapeutic target and biomarkers for counteracting this process.
Note: Versió postprint del document publicat a:
It is part of: Translational Research, The Journal of Laboratory and Clinical Medicine, 2016, vol. 178, p. 13-24.e5
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ISSN: 1931-5244
Appears in Collections:Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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