title: Young men with low birthweight exhibit decreased plasticity of genome-wide muscle DNA methylation by high-fat overfeeding.
abstract: OBJECTIVE
  The association between low birthweight (LBW) and risk of developing type 2 diabetes may involve epigenetic mechanisms, with skeletal muscle being a prime target tissue. Differential DNA methylation patterns have been observed in single genes in muscle tissue from type 2 diabetic and LBW individuals, and we recently showed multiple DNA methylation changes during short-term high-fat overfeeding in muscle of healthy people. In a randomised crossover study, we analysed genome-wide DNA promoter methylation in skeletal muscle of 17 young LBW men and 23 matched normal birthweight (NBW) men after a control and a 5 day high-fat overfeeding diet.
  
  
  METHODS
  DNA methylation was measured using Illumina's Infinium BeadArray covering 27,578 CpG sites representing 14,475 different genes.
  
  
  RESULTS
  After correction for multiple comparisons, DNA methylation levels were found to be similar in the LBW and NBW groups during the control diet. Whereas widespread DNA methylation changes were observed in the NBW group in response to high-fat overfeeding, only a few methylation changes were seen in the LBW group (χ(2), p < 0.001).
  
  
  CONCLUSIONS
  Our results indicate lower DNA methylation plasticity in skeletal muscle from LBW vs NBW men, potentially contributing to understanding the link between LBW and increased risk of type 2 diabetes.
authors.affiliation: Department of Endocrinology, Rigshospitalet, Tagensvej 20, Sec. 7652, 2200, Copenhagen N, Denmark.
authors.forename: Stine C
authors.initials: SC
authors.lastname: Jacobsen
authors.forename: Linn
authors.initials: L
authors.lastname: Gillberg
authors.forename: Jette
authors.initials: J
authors.lastname: Bork-Jensen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Ribel-Madsen
authors.forename: Ester
authors.initials: E
authors.lastname: Lara
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Calvanese
authors.forename: Charlotte
authors.initials: C
authors.lastname: Ling
authors.forename: Agustin F
authors.initials: AF
authors.lastname: Fernandez
authors.forename: Mario F
authors.initials: MF
authors.lastname: Fraga
authors.forename: Pernille
authors.initials: P
authors.lastname: Poulsen
authors.forename: Charlotte
authors.initials: C
authors.lastname: Brøns
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
mesh_terms: D000328:Adult; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics*; D000090205:DNA Methyltransferase 3A; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D059305:Diet, High-Fat / Q000009:adverse effects*; D044127:Epigenesis, Genetic / Q000235:genetics; D006801:Humans; D007230:Infant, Low Birth Weight / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D055815:Young Adult; D000097584:DNA Methyltransferase 3B
chemical_list: D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human