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Arachidonic and oleic acid exert distinct effects on the DNA methylome

Silva-Martínez, Guillermo A.; Rodríguez-Ríos, Dalia; Alvarado-Caudillo, Yolanda; Vaquero, Alejandro; Esteller, Manel; Carmona, F. Javier; Moran, Sebastian; Nielsen, Finn C.; Lindholm, Marie LU and Wrobel, Katarzyna, et al. (2016) In Epigenetics 11(5). p.321-334
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... (More)

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.

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published
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keywords
DNA methylation, epigenomics, fatty acid, PPAR, sirtuin, β-oxidation
in
Epigenetics
volume
11
issue
5
pages
14 pages
publisher
Landes Bioscience
external identifiers
  • scopus:84965060772
  • wos:000377274700001
ISSN
1559-2294
DOI
10.1080/15592294.2016.1161873
language
English
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yes
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141ac6ec-6b39-4ff3-a9d2-1f3388191349
date added to LUP
2016-09-29 11:28:40
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2017-04-30 17:37:43
@article{141ac6ec-6b39-4ff3-a9d2-1f3388191349,
  abstract     = {<p>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.</p>},
  author       = {Silva-Martínez, Guillermo A. and Rodríguez-Ríos, Dalia and Alvarado-Caudillo, Yolanda and Vaquero, Alejandro and Esteller, Manel and Carmona, F. Javier and Moran, Sebastian and Nielsen, Finn C. and Lindholm, Marie and Wrobel, Katarzyna and Wrobel, Kazimierz and Barbosa-Sabanero, Gloria and Zaina, Silvio and Lund, Gertrud},
  issn         = {1559-2294},
  keyword      = {DNA methylation,epigenomics,fatty acid,PPAR,sirtuin,β-oxidation},
  language     = {eng},
  month        = {05},
  number       = {5},
  pages        = {321--334},
  publisher    = {Landes Bioscience},
  series       = {Epigenetics},
  title        = {Arachidonic and oleic acid exert distinct effects on the DNA methylome},
  url          = {http://dx.doi.org/10.1080/15592294.2016.1161873},
  volume       = {11},
  year         = {2016},
}