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Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men

Jacobsen, S. C.; Brons, C.; Bork-Jensen, J.; Ribel-Madsen, R.; Yang, Beatrice LU ; Lara, E.; Hall, Elin LU ; Calvanese, V.; Nilsson, E. and Jorgensen, S. W., et al. (2012) In Diabetologia 55(12). p.3341-3349
Abstract
Energy-dense diets that are high in fat are associated with a risk of metabolic diseases. The underlying molecular mechanisms could involve epigenetics, as recent data show altered DNA methylation of putative type 2 diabetes candidate genes in response to high-fat diets. We examined the effect of a short-term high-fat overfeeding (HFO) diet on genome-wide DNA methylation patterns in human skeletal muscle. Skeletal muscle biopsies were obtained from 21 healthy young men after ingestion of a short-term HFO diet and a control diet, in a randomised crossover setting. DNA methylation was measured in 27,578 CpG sites/14,475 genes using Illumina's Infinium Bead Array. Candidate gene expression was determined by quantitative real-time PCR. HFO... (More)
Energy-dense diets that are high in fat are associated with a risk of metabolic diseases. The underlying molecular mechanisms could involve epigenetics, as recent data show altered DNA methylation of putative type 2 diabetes candidate genes in response to high-fat diets. We examined the effect of a short-term high-fat overfeeding (HFO) diet on genome-wide DNA methylation patterns in human skeletal muscle. Skeletal muscle biopsies were obtained from 21 healthy young men after ingestion of a short-term HFO diet and a control diet, in a randomised crossover setting. DNA methylation was measured in 27,578 CpG sites/14,475 genes using Illumina's Infinium Bead Array. Candidate gene expression was determined by quantitative real-time PCR. HFO introduced widespread DNA methylation changes affecting 6,508 genes (45%), with a maximum methylation change of 13.0 percentage points. The HFO-induced methylation changes were only partly and non-significantly reversed after 6-8 weeks. Alterations in DNA methylation levels primarily affected genes involved in inflammation, the reproductive system and cancer. Few gene expression changes were observed and these had poor correlation to DNA methylation. The genome-wide DNA methylation changes induced by the short-term HFO diet could have implications for our understanding of transient epigenetic regulation in humans and its contribution to the development of metabolic diseases. The slow reversibility suggests a methylation build-up with HFO, which over time may influence gene expression levels. (Less)
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keywords
DNA methylation, Epigenetic, Gene expression, Genome-wide, High-fat, overfeeding, Human, Illumina Infinium 27k Bead Array, Reversibility, Skeletal muscle, Type 2 diabetes
in
Diabetologia
volume
55
issue
12
pages
3341 - 3349
publisher
Springer Verlag
external identifiers
  • wos:000310381800022
  • scopus:84868211134
ISSN
1432-0428
DOI
10.1007/s00125-012-2717-8
language
English
LU publication?
yes
id
4b72588b-844d-45b3-9f48-7da15d629c5d (old id 3379424)
date added to LUP
2013-02-01 07:02:28
date last changed
2017-11-19 03:24:41
@article{4b72588b-844d-45b3-9f48-7da15d629c5d,
  abstract     = {Energy-dense diets that are high in fat are associated with a risk of metabolic diseases. The underlying molecular mechanisms could involve epigenetics, as recent data show altered DNA methylation of putative type 2 diabetes candidate genes in response to high-fat diets. We examined the effect of a short-term high-fat overfeeding (HFO) diet on genome-wide DNA methylation patterns in human skeletal muscle. Skeletal muscle biopsies were obtained from 21 healthy young men after ingestion of a short-term HFO diet and a control diet, in a randomised crossover setting. DNA methylation was measured in 27,578 CpG sites/14,475 genes using Illumina's Infinium Bead Array. Candidate gene expression was determined by quantitative real-time PCR. HFO introduced widespread DNA methylation changes affecting 6,508 genes (45%), with a maximum methylation change of 13.0 percentage points. The HFO-induced methylation changes were only partly and non-significantly reversed after 6-8 weeks. Alterations in DNA methylation levels primarily affected genes involved in inflammation, the reproductive system and cancer. Few gene expression changes were observed and these had poor correlation to DNA methylation. The genome-wide DNA methylation changes induced by the short-term HFO diet could have implications for our understanding of transient epigenetic regulation in humans and its contribution to the development of metabolic diseases. The slow reversibility suggests a methylation build-up with HFO, which over time may influence gene expression levels.},
  author       = {Jacobsen, S. C. and Brons, C. and Bork-Jensen, J. and Ribel-Madsen, R. and Yang, Beatrice and Lara, E. and Hall, Elin and Calvanese, V. and Nilsson, E. and Jorgensen, S. W. and Mandrup, S. and Ling, Charlotte and Fernandez, A. F. and Fraga, M. F. and Poulsen, P. and Vaag, A.},
  issn         = {1432-0428},
  keyword      = {DNA methylation,Epigenetic,Gene expression,Genome-wide,High-fat,overfeeding,Human,Illumina Infinium 27k Bead Array,Reversibility,Skeletal muscle,Type 2 diabetes},
  language     = {eng},
  number       = {12},
  pages        = {3341--3349},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men},
  url          = {http://dx.doi.org/10.1007/s00125-012-2717-8},
  volume       = {55},
  year         = {2012},
}