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

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Author

  • S. C. Jacobsen
  • C. Brons
  • J. Bork-Jensen
  • R. Ribel-Madsen
  • Beatrice Yang
  • E. Lara
  • Elin Hall
  • V. Calvanese
  • E. Nilsson
  • S. W. Jorgensen
  • S. Mandrup
  • Charlotte Ling
  • A. F. Fernandez
  • M. F. Fraga
  • P. Poulsen
  • A. Vaag
Show all

Summary, in English

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.

Publishing year

2012

Language

English

Pages

3341-3349

Publication/Series

Diabetologia

Volume

55

Issue

12

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • DNA methylation
  • Epigenetic
  • Gene expression
  • Genome-wide
  • High-fat
  • overfeeding
  • Human
  • Illumina Infinium 27k Bead Array
  • Reversibility
  • Skeletal muscle
  • Type 2 diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1432-0428