Article

Diabetologia

, Volume 55, Issue 12, pp 3341-3349

First online:

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

  • S. C. JacobsenAffiliated withSteno Diabetes CenterDepartment of Endocrinology, Rigshospitalet Email author 
  • , C. BrønsAffiliated withSteno Diabetes CenterDepartment of Endocrinology, Rigshospitalet
  • , J. Bork-JensenAffiliated withSteno Diabetes CenterDepartment of Endocrinology, Rigshospitalet
  • , R. Ribel-MadsenAffiliated withSteno Diabetes Center
  • , B. YangAffiliated withDepartment of Clinical Sciences, Lund University
  • , E. LaraAffiliated withCancer Epigenetics Group, National Cancer Centre
  • , E. HallAffiliated withDepartment of Clinical Sciences, Lund University
  • , V. CalvaneseAffiliated withCancer Epigenetics Group, National Cancer Centre
  • , E. NilssonAffiliated withSteno Diabetes Center
    • , S. W. JørgensenAffiliated withSteno Diabetes CenterDepartment of Endocrinology, Rigshospitalet
    • , S. MandrupAffiliated withDepartment of Biochemistry and Molecular Biology, University of Southern Denmark
    • , C. LingAffiliated withDepartment of Clinical Sciences, Lund University
    • , A. F. FernandezAffiliated withCancer Epigenetics Group, National Cancer Centre
    • , M. F. FragaAffiliated withCancer Epigenetics Group, National Cancer Centre
    • , P. PoulsenAffiliated withSteno Diabetes Center
    • , A. VaagAffiliated withSteno Diabetes CenterDepartment of Endocrinology, Rigshospitalet

Abstract

Aims/hypothesis

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.

Methods

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.

Results

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.

Conclusions/interpretation

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.

Keywords

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