title: Postweaning exposure to a high-fat diet is associated with alterations to the hepatic histone code in Japanese macaques.
abstract: BACKGROUND
  Expression of circadian gene, Npas2, is altered in fetal life with maternal high-fat (HF) diet exposure by virtue of alterations in the fetal histone code. We postulated that these disruptions would persist postnatally.
  
  
  METHODS
  Pregnant macaques were fed a control (CTR) or HF diet and delivered at term. When offspring were weaned, they were placed on either CTR or HF diet for a period of 5 mo to yield four exposure models (in utero diet/postweaning diet: CTR/CTR n = 5; CTR/HF n = 4; HF/CTR n = 4; and HF/HF n = 5). Liver specimens were obtained at necropsy at 1 y of age.
  
  
  RESULTS
  Hepatic trimethylation of lysine 4 of histone H3 is decreased (CTR/HF 0.87-fold, P = 0.038; HF/CTR 0.84-fold, P = 0.038), whereas hepatic methyltransferase activity increased by virtue of diet exposure (HF/HF 1.3-fold, P = 0.019). Using chromatin immunoprecipitation to determine Npas2 promoter occupancy, we found alterations of both repressive and permissive histone modifications specifically with postweaning HF diet exposure.
  
  
  CONCLUSIONS
  We found that altered Npas2 expression corresponds with a change in the histone code within the Npas2 promoter.
authors.affiliation: Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Suter
authors.forename: Diana
authors.initials: D
authors.lastname: Takahashi
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Grove
authors.forename: Kjersti M
authors.initials: KM
authors.lastname: Aagaard
mesh_terms: D000818:Animals; D015153:Blotting, Western; D047369:Chromatin Immunoprecipitation; D019175:DNA Methylation / Q000187:drug effects*; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D042421:Histone Code / Q000187:drug effects*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008251:Macaca; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D006657:Histones; D009419:Nerve Tissue Proteins; D006655:Histone Deacetylases