Arachidonic and oleic acid exert distinct effects on the DNA methylome

Research output: Contribution to journalArticle

Abstract

ABSTRACT: Abnormal fatty acid metabolism and availability are landmarks of metabolic diseases, which in turn are associated with aberrant DNA methylation profiles. To understand the role of fatty acids in disease epigenetics, we sought DNA methylation profiles specifically induced by arachidonic (AA) or oleic acid (OA) in cultured cells and compared those with published profiles of normal and diseased tissues. THP-1 monocytes were stimulated with AA or OA and analyzed using Infinium HumanMethylation450 BeadChip (Illumina) and Human Exon 1.0 ST array (Affymetrix). Data were corroborated in mouse embryonic fibroblasts. Comparisons with publicly available data were conducted by standard bioinformatics. AA and OA elicited a complex response marked by a general DNA hypermethylation and hypomethylation in the 1–200 μM range, respectively, with a maximal differential response at the 100 μM dose. The divergent response to AA and OA was prominent within the gene body of target genes, where it correlated positively with transcription. AA-induced DNA methylation profiles were similar to the corresponding profiles described for palmitic acid, atherosclerosis, diabetes, obesity, and autism, but relatively dissimilar from OA-induced profiles. Furthermore, human atherosclerosis grade-associated DNA methylation profiles were significantly enriched in AA-induced profiles. Biochemical evidence pointed to β-oxidation, PPAR-α, and sirtuin 1 as important mediators of AA-induced DNA methylation changes. In conclusion, AA and OA exert distinct effects on the DNA methylome. The observation that AA may contribute to shape the epigenome of important metabolic diseases, supports and expands current diet-based therapeutic and preventive efforts.

Details

Authors
  • Guillermo A. Silva-Martínez
  • Dalia Rodríguez-Ríos
  • Yolanda Alvarado-Caudillo
  • Alejandro Vaquero
  • Manel Esteller
  • F. Javier Carmona
  • Sebastian Moran
  • Finn C. Nielsen
  • Marie Lindholm
  • Katarzyna Wrobel
  • Kazimierz Wrobel
  • Gloria Barbosa-Sabanero
  • Silvio Zaina
  • Gertrud Lund
Organisations
External organisations
  • University of Guanajuato
  • Bellvitge Biomedical Research Institute
  • University of Copenhagen
  • National Polytechnic Institute
  • Skåne University Hospital
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Pharmacology and Toxicology

Keywords

  • DNA methylation, epigenomics, fatty acid, PPAR, sirtuin, β-oxidation
Original languageEnglish
Pages (from-to)321-334
Number of pages14
JournalEpigenetics
Volume11
Issue number5
Publication statusPublished - 2016 May 3
Publication categoryResearch
Peer-reviewedYes