Weight loss after gastric bypass surgery in human obesity remodels promoter methylation.

Abstract:

:DNA methylation provides a mechanism by which environmental factors can control insulin sensitivity in obesity. Here, we assessed DNA methylation in skeletal muscle from obese people before and after Roux-en-Y gastric bypass (RYGB). Obesity was associated with altered expression of a subset of genes enriched in metabolic process and mitochondrial function. After weight loss, the expression of the majority of the identified genes was normalized to levels observed in normal-weight, healthy controls. Among the 14 metabolic genes analyzed, promoter methylation of 11 genes was normalized to levels observed in the normal-weight, healthy subjects. Using bisulfite sequencing, we show that promoter methylation of PGC-1α and PDK4 is altered with obesity and restored to nonobese levels after RYGB-induced weight loss. A genome-wide DNA methylation analysis of skeletal muscle revealed that obesity is associated with hypermethylation at CpG shores and exonic regions close to transcription start sites. Our results provide evidence that obesity and RYGB-induced weight loss have a dynamic effect on the epigenome.

journal_name

Cell Rep

journal_title

Cell reports

authors

Barres R,Kirchner H,Rasmussen M,Yan J,Kantor FR,Krook A,Näslund E,Zierath JR

doi

10.1016/j.celrep.2013.03.018

subject

Has Abstract

pub_date

2013-04-25 00:00:00

pages

1020-7

issue

4

issn

2211-1247

pii

S2211-1247(13)00125-3

journal_volume

3

pub_type

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