title: Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark. annesille@hotmail.com
authors.forename: S C
authors.initials: SC
authors.lastname: Jacobsen
authors.forename: C
authors.initials: C
authors.lastname: Brøns
authors.forename: J
authors.initials: J
authors.lastname: Bork-Jensen
authors.forename: R
authors.initials: R
authors.lastname: Ribel-Madsen
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.forename: E
authors.initials: E
authors.lastname: Lara
authors.forename: E
authors.initials: E
authors.lastname: Hall
authors.forename: V
authors.initials: V
authors.lastname: Calvanese
authors.forename: E
authors.initials: E
authors.lastname: Nilsson
authors.forename: S W
authors.initials: SW
authors.lastname: Jørgensen
authors.forename: S
authors.initials: S
authors.lastname: Mandrup
authors.forename: C
authors.initials: C
authors.lastname: Ling
authors.forename: A F
authors.initials: AF
authors.lastname: Fernandez
authors.forename: M F
authors.initials: MF
authors.lastname: Fraga
authors.forename: P
authors.initials: P
authors.lastname: Poulsen
authors.forename: A
authors.initials: A
authors.lastname: Vaag
mesh_terms: D027682:Cation Transport Proteins / Q000235:genetics; D018899:CpG Islands / Q000235:genetics; D018592:Cross-Over Studies; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D059305:Diet, High-Fat; D044127:Epigenesis, Genetic; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D044343:Overnutrition; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D015534:Trans-Activators / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult; D000075703:Zinc Transporter 8
chemical_list: C493966:CDKN2B protein, human; D027682:Cation Transport Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D006360:Heat-Shock Proteins; D018398:Homeodomain Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C492522:SLC30A8 protein, human; D015534:Trans-Activators; D014157:Transcription Factors; D000075703:Zinc Transporter 8; C084010:pancreatic and duodenal homeobox 1 protein; C494921:AKT2 protein, human; D051057:Proto-Oncogene Proteins c-akt