Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men
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.
- blah 125_2012_2717_MOESM1_ESM.pdf (34KB)
- blah 125_2012_2717_MOESM2_ESM.pdf (51KB)
- blah 125_2012_2717_MOESM3_ESM.pdf (23KB)
- blah 125_2012_2717_MOESM4_ESM.pdf (73KB)
- blah 125_2012_2717_MOESM5_ESM.pdf (94KB)
- blah 125_2012_2717_MOESM6_ESM.pdf (98KB)
- blah 125_2012_2717_MOESM7_ESM.pdf (43KB)
- blah 125_2012_2717_MOESM8_ESM.pdf (18KB)
- blah 125_2012_2717_MOESM9_ESM.pdf (16KB)
- Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men
Volume 55, Issue 12 , pp 3341-3349
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- DNA methylation
- Gene expression
- High-fat overfeeding
- Illumina Infinium 27k Bead Array
- Skeletal muscle
- Type 2 diabetes
- Industry Sectors
- Author Affiliations
- 1. Steno Diabetes Center, Gentofte, Denmark
- 2. Department of Endocrinology, Rigshospitalet, Tagensvej 20, Sec. 7652, 2200, Copenhagen N, Denmark
- 3. Department of Clinical Sciences, Lund University, Malmö, Sweden
- 4. Cancer Epigenetics Group, National Cancer Centre, Madrid, Spain
- 5. Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark