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

TY - JOUR

T1 - Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men

AU - Jacobsen, S C

AU - Brøns, Charlotte

AU - Bork-Jensen, Jette

AU - Ribel-Madsen, Rasmus

AU - Yang, B

AU - Lara, E

AU - Hall, E

AU - Calvanese, V

AU - Nilsson, E

AU - Jørgensen, S W

AU - Mandrup, S

AU - Ling, C

AU - Fernandez, A F

AU - Fraga, M F

AU - Poulsen, P

AU - Vaag, A

N1 - IHE 2012 074

PY - 2012/12

Y1 - 2012/12

N2 - 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 6-8weeks.Alterations inDNAmethylation 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.

AB - 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 6-8weeks.Alterations inDNAmethylation 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.

U2 - 10.1007/s00125-012-2717-8

DO - 10.1007/s00125-012-2717-8

M3 - Journal article

C2 - 22961225

SN - 0012-186X

VL - 55

SP - 3341

EP - 3349

JO - Diabetologia

JF - Diabetologia

IS - 12

ER -