Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation
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 gene...
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2013-04-01
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Series: | Cell Reports |
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doaj-d4723d00a2e943e19f57c7b3ef149a312020-11-24T21:29:07ZengElsevierCell Reports2211-12472013-04-01341020102710.1016/j.celrep.2013.03.018Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter MethylationRomain Barres0Henriette Kirchner1Morten Rasmussen2Jie Yan3Francisc R. Kantor4Anna Krook5Erik Näslund6Juleen R. Zierath7Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, SwedenDepartment of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, SwedenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, DenmarkDepartment of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, SwedenThe Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, DenmarkDepartment of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, SwedenDivision of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, SE-171 77 Stockholm, SwedenDepartment of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden 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. http://www.sciencedirect.com/science/article/pii/S2211124713001253 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Romain Barres Henriette Kirchner Morten Rasmussen Jie Yan Francisc R. Kantor Anna Krook Erik Näslund Juleen R. Zierath |
spellingShingle |
Romain Barres Henriette Kirchner Morten Rasmussen Jie Yan Francisc R. Kantor Anna Krook Erik Näslund Juleen R. Zierath Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation Cell Reports |
author_facet |
Romain Barres Henriette Kirchner Morten Rasmussen Jie Yan Francisc R. Kantor Anna Krook Erik Näslund Juleen R. Zierath |
author_sort |
Romain Barres |
title |
Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation |
title_short |
Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation |
title_full |
Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation |
title_fullStr |
Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation |
title_full_unstemmed |
Weight Loss after Gastric Bypass Surgery in Human Obesity Remodels Promoter Methylation |
title_sort |
weight loss after gastric bypass surgery in human obesity remodels promoter methylation |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2013-04-01 |
description |
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.
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url |
http://www.sciencedirect.com/science/article/pii/S2211124713001253 |
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