title: Critical periods of increased fetal vulnerability to a maternal high fat diet.
abstract: BACKGROUND
  Fetal adaptations to high fat (HF) diet in utero (IU) that may predispose to Metabolic Syndrome (MetS) in adulthood include changes in fetal hepatic gene expression. Studies were performed to determine whether maternal exposure to HF diet at different stages during pregnancy had different effects on the fetus, including hepatic gene expression.
  
  
  METHODS
  Female wild type mice were fed either a HF or breeding chow (C) for 2 wks prior to mating. The experimental groups were composed of embryonic day (e) 18.5 fetuses obtained from WT female mice that were fed HF (HF, 35.5% fat) or breeding chow (C, 9.5% fat) for 2 wk before mating until e9.5 of pregnancy (periconception-midpregnancy). At e9.5 dams were switched to the opposite diet (C-HF or HF-C).
  
  
  RESULTS
  Exposure to HF diet throughout pregnancy reduced maternal weight gain compared to C diet (p < 0.02 HF vs. C). HF-C dams had significantly decreased adiponectin levels and litter size when compared to C-HF (p < 0.02 HF-C vs C-HF). Independent of the timing of exposure to HF, fetal weight and length were significantly decreased when compared to C diet (HF, C-HF and HF-C vs. C p < 0.02). HF diet during the second half of pregnancy increased expression of genes in the fetal liver associated with fetal growth (C-HF vs C p < 0.001), glucose production (C-HF vs C p < 0.04), oxidative stress and inflammation (C-HF vs C p < 0.01) compared to C diet.
  
  
  CONCLUSIONS
  This model defines that there are critical periods during gestation in which the fetus is actively shaped by the environment. Early exposure to a HF diet determines litter size while exposure to HF during the second half of pregnancy leads to dysregulation of expression of key genes responsible for fetal growth, hepatic glucose production and oxidative stress. These findings underscore the importance of future studies designed to clarify how these critical periods may influence future risk of developing MetS later in life.
authors.forename: Maria del Mar
authors.initials: Mdel M
authors.lastname: Plata
authors.forename: Lyda
authors.initials: L
authors.lastname: Williams
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Seki
authors.forename: Kirsten
authors.initials: K
authors.lastname: Hartil
authors.forename: Harpreet
authors.initials: H
authors.lastname: Kaur
authors.forename: Chia-Lei
authors.initials: CL
authors.lastname: Lin
authors.forename: Ariana
authors.initials: A
authors.lastname: Fiallo
authors.forename: Alan S
authors.initials: AS
authors.lastname: Glenn
authors.forename: Ellen B
authors.initials: EB
authors.lastname: Katz
authors.forename: Mamta
authors.initials: M
authors.lastname: Fuloria
authors.affiliation: Department of Pediatrics, Albert Einstein College of Medicine, 10461 Bronx, NY, USA. maureen.charron@einstein.yu.edu.
authors.forename: Maureen J
authors.initials: MJ
authors.lastname: Charron
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Vuguin
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D021461:Animals, Outbred Strains; D003433:Crosses, Genetic; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D047109:Fetal Development; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D020567:Fetal Weight; D018507:Gene Expression Regulation, Developmental; D005943:Gluconeogenesis; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006943:Hyperglycemia / Q000196:embryology / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D008098:Litter Size; D008099:Liver / Q000196:embryology / Q000276:immunology / Q000378:metabolism; D039382:Maternal Nutritional Physiological Phenomena; D024821:Metabolic Syndrome / Q000196:embryology / Q000209:etiology* / Q000276:immunology / Q000378:metabolism; D008817:Mice, Mutant Strains; D018384:Oxidative Stress
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D051275:Glucose Transporter Type 4; C495693:Slc2a4 protein, mouse