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

TY - JOUR

T1 - Weight loss after gastric bypass surgery in human obesity remodels promoter methylation

AU - Barres, Romain

AU - Kirchner, Henriette

AU - Rasmussen, Morten

AU - Yan, Jie

AU - Kantor, Francisc R

AU - Krook, Anna

AU - Näslund, Erik

AU - Zierath, Juleen R

N1 - Erratum to Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation [Cell Reports 3, (2013) 1020-1027] https://doi.org/10.1016/j.celrep.2013.05.017

PY - 2013/4/25

Y1 - 2013/4/25

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2013.03.018

DO - 10.1016/j.celrep.2013.03.018

M3 - Journal article

C2 - 23583180

SN - 2211-1247

VL - 3

SP - 1020

EP - 1027

JO - Cell Reports

JF - Cell Reports

IS - 4

ER -