title: Maternal folate depletion during early development and high fat feeding from weaning elicit similar changes in gene expression, but not in DNA methylation, in adult offspring.
abstract: The 'Predictive Adaptive Response' hypothesis suggests that the in utero environment when mismatched with the post-natal environment can influence later life health. Underlying mechanisms are poorly understood, but may involve gene transcription changes regulated via epigenetic mechanisms.
  
  
  
  In a 2 × 2 factorial design, female C57Bl/6 mice were randomised to low or normal folate diets (0.4 mg/2 mg folic acid/kg diet) prior to and during pregnancy and lactation with offspring randomised to high- or low-fat diets at weaning. Genome-wide gene expression and promoter DNA methylation were measured using microarrays in adult male livers. Maternal folate depletion and high fat intake post-weaning influenced gene expression (1859 and 1532 genes, respectively) and promoter DNA methylation (201 and 324 loci, respectively) but changes in expression and methylation were poorly matched for both dietary interventions. Expression of 642 genes was altered in response to both maternal folate depletion and post-weaning high fat feeding, treatments imposed separately. In addition, there was evidence that the combined dietary insult (i.e. maternal folate depletion followed by high fat post-weaning) caused the largest expression change for most genes.
  
  
  
  Our observations align with, and provide evidence in support of, a potential underlying mechanism for the 'Predictive Adaptive Response' hypothesis.
authors.affiliation: Human Nutrition Research Centre, Institute for Health and Society, Newcastle University, UK.
authors.forename: Jill A
authors.initials: JA
authors.lastname: McKay
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, UK.
authors.forename: Long
authors.initials: L
authors.lastname: Xie
authors.affiliation: Maastricht Centre for Systems Biology, Maastricht, The Netherlands.
authors.forename: Michiel
authors.initials: M
authors.lastname: Adriaens
authors.affiliation: Department of Bioinformatics - BiGCaT, Maastricht University, Maastricht, The Netherlands.
authors.forename: Chris T
authors.initials: CT
authors.lastname: Evelo
authors.affiliation: Human Nutrition Research Centre, Institute for Cell and Molecular Biosciences, Newcastle University, UK.|Faculty of Health and Life Sciences, Northumbria University, UK.
authors.forename: Dianne
authors.initials: D
authors.lastname: Ford
authors.affiliation: Human Nutrition Research Centre, Institute of Cellular Medicine, Newcastle University, UK.
authors.forename: John C
authors.initials: JC
authors.lastname: Mathers
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D011247:Pregnancy; D001835:Body Weight / Q000235:genetics; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat; D019175:DNA Methylation / Q000502:physiology; D044127:Epigenesis, Genetic; D005247:Feeding Behavior; D005492:Folic Acid / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D007774:Lactation; D008099:Liver / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D008810:Mice, Inbred C57BL; D011401:Promoter Regions, Genetic; D014886:Weaning
chemical_list: D005492:Folic Acid
keywords: DNA methylation; Early life nutrition; Folate depletion; Gene expression; High-fat diet; Liver