title: The trans fatty acid elaidate affects the global DNA methylation profile of cultured cells and in vivo.
abstract: BACKGROUND
  The deleterious effects of dietary trans fatty acids (tFAs) on human health are well documented. Although significantly reduced or banned in various countries, tFAs may trigger long-term responses that would represent a valid human health concern, particularly if tFAs alter the epigenome.
  
  
  METHODS
  Based on these considerations, we asked whether the tFA elaidic acid (EA; tC18:1) has any effects on global DNA methylation and the transcriptome in cultured human THP-1 monocytes, and whether the progeny of EA-supplemented dams during either pregnancy or lactation in mice (n = 20 per group) show any epigenetic change after exposure.
  
  
  RESULTS
  EA induced a biphasic effect on global DNA methylation in THP-1 cells, i.e. hypermethylation in the 1-50 μM concentration range, followed by hypomethylation up to the 200 μM dose. On the other hand, the cis isomer oleic acid (OA), a fatty acid with documented beneficial effects on human health, exerted a distinct response, i.e. its effects were weaker and only partially overlapping with EA's. The maximal differential response between EA and OA was observed at the 50 μM dose. Array expression data revealed that EA induced a pro-inflammatory and adipogenic transcriptional profile compared with OA, although with modest effects on selected (n = 9) gene promoter methylation. In mice, maternal EA supplementation in utero or via the breastmilk induced global adipose tissue DNA hypermethylation in the progeny, that was detectable postnatally at the age of 3 months.
  
  
  CONCLUSIONS
  We document that global DNA hypermethylation is a specific and consistent response to EA in cell culture and in mice, and that EA may exert long-term effects on the epigenome following maternal exposure.
authors.affiliation: Department of Medical Sciences, Division of Health Sciences, Leon Campus, University of Guanajuato, Leon, Gto., Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Flores-Sierra
authors.affiliation: Department of Medical Sciences, Division of Health Sciences, Leon Campus, University of Guanajuato, Leon, Gto., Mexico.|Tecnológico de Monterrey, Leon Campus, Leon, Gto., Mexico.
authors.forename: Martín
authors.initials: M
authors.lastname: Arredondo-Guerrero
authors.affiliation: Department of Genetic Engineering, CINVESTAV Irapuato Unit, 36821, Irapuato, Gto., Mexico.
authors.forename: Braulio
authors.initials: B
authors.lastname: Cervantes-Paz
authors.affiliation: Department of Genetic Engineering, CINVESTAV Irapuato Unit, 36821, Irapuato, Gto., Mexico.
authors.forename: Dalia
authors.initials: D
authors.lastname: Rodríguez-Ríos
authors.affiliation: Department of Medical Sciences, Division of Health Sciences, Leon Campus, University of Guanajuato, Leon, Gto., Mexico.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Alvarado-Caudillo
authors.affiliation: Center for Genomic Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Finn C
authors.initials: FC
authors.lastname: Nielsen
authors.affiliation: Department of Chemistry, Division of Natural and Exact Sciences, Guanajuato Campus, University of Guanajuato, Guanajuato, Gto., Mexico.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wrobel
authors.affiliation: Department of Chemistry, Division of Natural and Exact Sciences, Guanajuato Campus, University of Guanajuato, Guanajuato, Gto., Mexico.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Wrobel
authors.affiliation: Department of Medical Sciences, Division of Health Sciences, Leon Campus, University of Guanajuato, Leon, Gto., Mexico.
authors.forename: Silvio
authors.initials: S
authors.lastname: Zaina
authors.affiliation: Department of Genetic Engineering, CINVESTAV Irapuato Unit, 36821, Irapuato, Gto., Mexico. glund@ira.cinvestav.mx.
authors.forename: Gertrud
authors.initials: G
authors.lastname: Lund
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects; D000818:Animals; D002478:Cells, Cultured; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006801:Humans; D007774:Lactation; D008297:Male; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects; D019301:Oleic Acid / Q000009:adverse effects* / Q000494:pharmacology; D009829:Oleic Acids; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
chemical_list: D009829:Oleic Acids; D019301:Oleic Acid; C011459:elaidic acid
keywords: DNA methylation; Elaidic acid; Mouse model; Oleic acid; THP-1 cell line; Whole genome expression