title: Prenatal polycyclic aromatic hydrocarbon, adiposity, peroxisome proliferator-activated receptor (PPAR) γ methylation in offspring, grand-offspring mice.
abstract: BACKGROUND
  Greater levels of prenatal exposure to polycyclic aromatic hydrocarbon (PAH) have been associated with childhood obesity in epidemiological studies. However, the underlying mechanisms are unclear.
  
  
  OBJECTIVE
  We hypothesized that prenatal PAH over-exposure during gestation would lead to weight gain and increased fat mass in offspring and grand-offspring mice. Further, we hypothesized that altered adipose gene expression and DNA methylation in genes important to adipocyte differentiation would be affected.
  
  
  METHODS
  Pregnant dams were exposed to a nebulized PAH mixture versus negative control aerosol 5 days a week, for 3 weeks. Body weight was recorded from postnatal day (PND) 21 through PND60. Body composition, adipose cell size, gene expression of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/enhancer-binding proteins (C/EBP) α, cyclooxygenase (Cox)-2, fatty acid synthase (FAS) and adiponectin, and DNA methylation of PPAR γ, were assayed in both the offspring and grand-offspring adipose tissue.
  
  
  RESULTS
  Offspring of dams exposed to greater PAH during gestation had increased weight, fat mass, as well as higher gene expression of PPAR γ, C/EBP α, Cox2, FAS and adiponectin and lower DNA methylation of PPAR γ. Similar differences in phenotype and DNA methylation extended through the grand-offspring mice.
  
  
  CONCLUSIONS
  Greater prenatal PAH exposure was associated with increased weight, fat mass, adipose gene expression and epigenetic changes in progeny.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors.forename: Zhonghai
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors.forename: Hanjie
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors.forename: Christina
authors.initials: C
authors.lastname: Maher
authors.affiliation: Division of Pediatric Pulmonary, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors.forename: Emilio
authors.initials: E
authors.lastname: Arteaga-Solis
authors.affiliation: Department of Psychology, Columbia University, New York, New York, United States of America.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Champagne
authors.affiliation: Departments of Medicine and Neuroscience, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
authors.forename: Licheng
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Toxicology, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: McDonald
authors.affiliation: Lamont-Doherty Earth Observatory, Columbia University, Palisades, New York, United States of America.
authors.forename: Beizhan
authors.initials: B
authors.lastname: Yan
authors.affiliation: Departments of Medicine and Neuroscience, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, New York, United States of America.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Schwartz
authors.affiliation: Division of Pulmonary, Allergy and Critical Care of Medicine, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America; Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, New York, United States of America; Division of Pediatric Allergy, Immunology and Rheumatology, Department of Pediatrics, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Miller
mesh_terms: D017667:Adipocytes / Q000166:cytology; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D050154:Adiposity / Q000187:drug effects* / Q000235:genetics*; D000818:Animals; D001835:Body Weight / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D048429:Cell Size; D018899:CpG Islands; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D018811:Maternal Exposure; D051379:Mice; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D063766:Pediatric Obesity / Q000209:etiology / Q000378:metabolism; D010641:Phenotype; D011084:Polycyclic Aromatic Hydrocarbons / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; D022762:CCAAT-Enhancer-Binding Proteins; D047495:PPAR gamma; D011084:Polycyclic Aromatic Hydrocarbons; D019014:fas Receptor; D051546:Cyclooxygenase 2