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Title: Arachidonic and oleic acid exert distinct effects on the DNA methylome
Author: Silva-Martínez, Guillermo A.
Rodríguez-Ríos, Dalia
Alvarado-Caudillo, Yolanda
Vaquero García, Alejandro
Esteller, Manel
Carmona, F. Javier
Moran, Sebastian
Nielsen, Finn C.
Wickström-Lindholm, Marie
Wrobel, Katarzyna
Barbosa-Sabanero, Gloria
Zaina, Silvio
Lund, Gertrud
Keywords: Àcid araquidònic
Àcid oleic
Àcids grassos en la nutrició
Arachidonic acid
Oleic acid
Fatty acids in human nutrition
Issue Date: 3-May-2016
Publisher: Landes Bioscience
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.
Note: Versió postprint del document publicat a:
It is part of: Epigenetics, 2016, vol. 11, num. 5, p. 321-334
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ISSN: 1559-2294
Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (Ciències Fisiològiques)

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