El pròxim dijous 7 de maig, el Dipòsit Digital no estarà operatiu de 8:00 a 12:00 h per tasques d'actualització. Disculpeu les molèsties.
El próximo jueves 7 de mayo, el Dipòsit Digital no estará operativo de 8:00 a 12:00 h debido a tareas de actualización. Disculpen las molestias.
Our digital repository will be temporarily unavailable on Thursday, May 7th, from 8:00 a.m. to 12:00 p.m. due to a system update.

Fitxers

668671.pdf (2.29 MB)

Tipus de document

Article

Versió

Versió acceptada

Data de publicació

2016-07-14

Llicència de publicació

cc-by-nc-nd (c) Central Society for Clinical Research , 2016
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/111363

Genome-wide DNA methylation pattern in visceral adipose tissue differentiates insulin-resistant from insulin-sensitive obese subject

Títol de la revista

Autors

Director/Tutor

ISSN de la revista

Títol del volum

Recurs relacionat

https://doi.org/10.1016/j.trsl.2016.07.002

Resum

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.

Matèries

ADN, Metilació, Epigènesi, Teixit adipós, Resistència a la insulina, Diabetis no-insulinodependent, Obesitat mòrbida

Matèries (anglès)

DNA, Methylation, Epigenesis, Adipose tissues, Insulin resistance, Non-insulin-dependent diabetes, Morbid obesity

Citació

Col·leccions

Articles publicats en revistes (Ciències Fisiològiques)
Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

Citació

CRUJEIRAS, Ana B., et al. Genome-wide DNA methylation pattern in visceral adipose tissue differentiates insulin-resistant from insulin-sensitive obese subject. Translational Research. The Journal of Laboratory and Clinical Medicine. Vol.  2016, núm. 178, pàgs. 13-24. ISSN 1931-5244. [consulta: 7 de maig de 2026]. Disponible a: https://hdl.handle.net/2445/111363

Exportar metadades

JSON - METS

Compartir registre