2026-04-13T02:45:29Zhttps://recercat.cat/oai/request
oai:recercat.cat:2445/1113632025-12-05T09:25:00Zcom_2072_1057col_2072_478799col_2072_478916col_2072_478917
RECERCAT author Crujeiras, Ana B. author Diaz-Lagares, Angel author Moreno-Navarrete, José María author Sandoval, Juan author Hervas, David author Gomez, A. author Ricart Engel, Wifredo author Casanueva, Felipe F. author Esteller, Manel author Fernandez-Real, J. M. 2017-05-22T08:10:28Z2017-07-14T22:01:20Z2016-07-142017-05-22T08:10:28Z 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. cc-by-nc-nd (c) Central Society for Clinical Research , 2016 http://creativecommons.org/licenses/by-nc-nd/3.0/es info:eu-repo/semantics/openAccess ADN Metilació Epigènesi Teixit adipós Resistència a la insulina Diabetis no-insulinodependent Obesitat mòrbida DNA Methylation Epigenesis Adipose tissues Insulin resistance Non-insulin-dependent diabetes Morbid obesity Genome-wide DNA methylation pattern in visceral adipose tissue differentiates insulin-resistant from insulin-sensitive obese subject info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion