Arachidonic and oleic acid exert distinct effects on the DNA methylome

Guillermo A. Silva-Martínez; Dalia Rodríguez-Ríos; Yolanda Alvarado-Caudillo; Alejandro Vaquero; Manel Esteller; F. Javier Carmona; Sebastian Moran; Finn C. Nielsen; Marie Wickström-Lindholm; Katarzyna Wrobel; Kazimierz Wrobel; Gloria Barbosa-Sabanero; Silvio Zaina; Gertrud Lund

doi:10.1080/15592294.2016.1161873

Arachidonic and oleic acid exert distinct effects on the DNA methylome

Guillermo A. Silva-Martínez, Dalia Rodríguez-Ríos, Yolanda Alvarado-Caudillo, Alejandro Vaquero, Manel Esteller, F. Javier Carmona, Sebastian Moran, Finn C. Nielsen, Marie Wickström-Lindholm, Katarzyna Wrobel, Kazimierz Wrobel, Gloria Barbosa-Sabanero, Silvio Zaina, Gertrud Lund^*

^*Corresponding author for this work

Department of Clinical Medicine

33 Citations (Scopus)

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.

Original language	English
Journal	Epigenetics
Volume	11
Issue number	5
Pages (from-to)	321-334
Number of pages	14
ISSN	1559-2294
DOIs	https://doi.org/10.1080/15592294.2016.1161873
Publication status	Published - 2016

Keywords

DNA methylation
epigenomics
fatty acid
PPAR
sirtuin
β-oxidation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Silva-Martínez, G. A., Rodríguez-Ríos, D., Alvarado-Caudillo, Y., Vaquero, A., Esteller, M., Carmona, F. J., Moran, S., Nielsen, F. C., Wickström-Lindholm, M., Wrobel, K., Wrobel, K., Barbosa-Sabanero, G., Zaina, S., & Lund, G. (2016). Arachidonic and oleic acid exert distinct effects on the DNA methylome. Epigenetics, 11(5), 321-334. https://doi.org/10.1080/15592294.2016.1161873

Silva-Martínez, GA, Rodríguez-Ríos, D, Alvarado-Caudillo, Y, Vaquero, A, Esteller, M, Carmona, FJ, Moran, S, Nielsen, FC, Wickström-Lindholm, M, Wrobel, K, Wrobel, K, Barbosa-Sabanero, G, Zaina, S & Lund, G 2016, 'Arachidonic and oleic acid exert distinct effects on the DNA methylome', Epigenetics, vol. 11, no. 5, pp. 321-334. https://doi.org/10.1080/15592294.2016.1161873

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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.",

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author = "Silva-Mart{\'i}nez, {Guillermo A.} and Dalia Rodr{\'i}guez-R{\'i}os and Yolanda Alvarado-Caudillo and Alejandro Vaquero and Manel Esteller and Carmona, {F. Javier} and Sebastian Moran and Nielsen, {Finn C.} and Marie Wickstr{\"o}m-Lindholm and Katarzyna Wrobel and Kazimierz Wrobel and Gloria Barbosa-Sabanero and Silvio Zaina and Gertrud Lund",

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T1 - Arachidonic and oleic acid exert distinct effects on the DNA methylome

AU - Silva-Martínez, Guillermo A.

AU - Rodríguez-Ríos, Dalia

AU - Alvarado-Caudillo, Yolanda

AU - Vaquero, Alejandro

AU - Esteller, Manel

AU - Carmona, F. Javier

AU - Moran, Sebastian

AU - Nielsen, Finn C.

AU - Wickström-Lindholm, Marie

AU - Wrobel, Katarzyna

AU - Wrobel, Kazimierz

AU - Barbosa-Sabanero, Gloria

AU - Zaina, Silvio

AU - Lund, Gertrud

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - DNA methylation

KW - epigenomics

KW - fatty acid

KW - PPAR

KW - sirtuin

KW - β-oxidation

U2 - 10.1080/15592294.2016.1161873

DO - 10.1080/15592294.2016.1161873

M3 - Journal article

C2 - 27088456

AN - SCOPUS:84965060772

SN - 1559-2294

VL - 11

SP - 321

EP - 334

JO - Epigenetics

JF - Epigenetics

IS - 5

ER -

Arachidonic and oleic acid exert distinct effects on the DNA methylome

Abstract

Keywords

UN SDGs

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