Prenatal polycyclic aromatic hydrocarbon, adiposity, peroxisome proliferator-activated receptor (PPAR) γ methylation in offspring, grand-offspring mice

Zhonghai Yan, Hanjie Zhang, Christina Maher, Emilio Arteaga-Solis, Frances A. Champagne, Licheng Wu, Jacob D. McDonald, Beizhan Yan, Gary J. Schwartz, Rachel L. Miller

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Rationale: 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.

Objectives: 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.

Materials and 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.

Findings: 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.

Original languageEnglish (US)
Article numbere110706
JournalPloS one
Volume9
Issue number10
DOIs
StatePublished - Oct 27 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yan, Z., Zhang, H., Maher, C., Arteaga-Solis, E., Champagne, F. A., Wu, L., McDonald, J. D., Yan, B., Schwartz, G. J., & Miller, R. L. (2014). Prenatal polycyclic aromatic hydrocarbon, adiposity, peroxisome proliferator-activated receptor (PPAR) γ methylation in offspring, grand-offspring mice. PloS one, 9(10), [e110706]. https://doi.org/10.1371/journal.pone.0110706