title: Methyl vitamins contribute to obesogenic effects of a high multivitamin gestational diet and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring.
abstract: METHODS
  High multivitamin (HV, tenfold AIN-93G) gestational diets fed to Wistar rats increase food intake, obesity, and characteristics of metabolic syndrome in the offspring. We hypothesized that methyl vitamins, and specifically folate, in the HV gestational diet contribute to the obesogenic phenotypes consistent with their epigenetic effects on hypothalamic food intake regulatory mechanisms.
  
  
  RESULTS
  Male offspring of dams fed the AIN-93G diet with high methyl vitamins (HMethyl; tenfold folate, vitamins B12, and B6) (Study 1) and HV with recommended folate (HVRF) (Study 2) were compared with those from HV and recommended vitamin (RV) fed dams. All offspring were weaned to a high fat diet for 8 wks. HMethyl diet, similar to HV, and compared to RV, resulted in higher food intake, body weight, and metabolic disturbances. Removing folate additions to the HV diet in HVRF offspring normalized the obesogenic phenotype. Methyl vitamins, and folate in HV diets, altered hypothalamic gene expression toward increased food intake concurrent with DNA methylation and leptin and insulin receptor signaling dysfunction.
  
  
  CONCLUSIONS
  Methyl vitamins in HV gestational diets contribute to obesogenic phenotypes and epigenetic alterations in the hypothalamic feeding pathways in the offspring. Folate alone accounts for many of these effects.
authors.affiliation: Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Clara E
authors.initials: CE
authors.lastname: Cho
authors.forename: Emanuela
authors.initials: E
authors.lastname: Pannia
authors.forename: Pedro S P
authors.initials: PS
authors.lastname: Huot
authors.forename: Diana
authors.initials: D
authors.lastname: Sánchez-Hernández
authors.forename: Ruslan
authors.initials: R
authors.lastname: Kubant
authors.forename: David W
authors.initials: DW
authors.lastname: Dodington
authors.forename: Wendy E
authors.initials: WE
authors.lastname: Ward
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bazinet
authors.forename: G Harvey
authors.initials: GH
authors.lastname: Anderson
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D019175:DNA Methylation; D004032:Diet; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D005492:Folic Acid / Q000009:adverse effects / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects; D020738:Leptin / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D009765:Obesity / Q000209:etiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017208:Rats, Wistar; D014805:Vitamin B 12; D014815:Vitamins / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology; D014886:Weaning
chemical_list: D020738:Leptin; D014815:Vitamins; D005492:Folic Acid; D014805:Vitamin B 12
keywords: DNA methylation; Folate; Gestation; Methyl vitamins; Obesity