The trans fatty acid elaidate affects the global DNA methylation profile of cultured cells and in vivo

José Flores-Sierra; Martín Arredondo-Guerrero; Braulio Cervantes-Paz; Dalia Rodríguez-Ríos; Yolanda Alvarado-Caudillo; Finn C. Nielsen; Katarzyna Wrobel; Kazimierz Wrobel; Silvio Zaina; Gertrud Lund

doi:10.1186/s12944-016-0243-2

The trans fatty acid elaidate affects the global DNA methylation profile of cultured cells and in vivo

José Flores-Sierra, Martín Arredondo-Guerrero, Braulio Cervantes-Paz, Dalia Rodríguez-Ríos, Yolanda Alvarado-Caudillo, Finn C. Nielsen, Katarzyna Wrobel, Kazimierz Wrobel, Silvio Zaina, Gertrud Lund^*

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

18 Citationer (Scopus)

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. Conclusion: 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.

Originalsprog	Engelsk
Artikelnummer	75
Tidsskrift	Lipids in Health and Disease
Vol/bind	15
Antal sider	7
ISSN	1476-511X
DOI	https://doi.org/10.1186/s12944-016-0243-2
Status	Udgivet - 12 apr. 2016

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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. Conclusion: 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.",

keywords = "DNA methylation, Elaidic acid, Mouse model, Oleic acid, THP-1 cell line, Whole genome expression",

author = "Jos{\'e} Flores-Sierra and Mart{\'i}n Arredondo-Guerrero and Braulio Cervantes-Paz and Dalia Rodr{\'i}guez-R{\'i}os and Yolanda Alvarado-Caudillo and Nielsen, {Finn C.} and Katarzyna Wrobel and Kazimierz Wrobel and Silvio Zaina and Gertrud Lund",

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doi = "10.1186/s12944-016-0243-2",

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journal = "Lipids in Health and Disease",

issn = "1476-511X",

publisher = "BioMed Central",

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TY - JOUR

T1 - The trans fatty acid elaidate affects the global DNA methylation profile of cultured cells and in vivo

AU - Flores-Sierra, José

AU - Arredondo-Guerrero, Martín

AU - Cervantes-Paz, Braulio

AU - Rodríguez-Ríos, Dalia

AU - Alvarado-Caudillo, Yolanda

AU - Nielsen, Finn C.

AU - Wrobel, Katarzyna

AU - Wrobel, Kazimierz

AU - Zaina, Silvio

AU - Lund, Gertrud

PY - 2016/4/12

Y1 - 2016/4/12

N2 - 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. Conclusion: 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.

AB - 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. Conclusion: 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.

KW - DNA methylation

KW - Elaidic acid

KW - Mouse model

KW - Oleic acid

KW - THP-1 cell line

KW - Whole genome expression

U2 - 10.1186/s12944-016-0243-2

DO - 10.1186/s12944-016-0243-2

M3 - Journal article

C2 - 27068706

AN - SCOPUS:84966377324

SN - 1476-511X

VL - 15

JO - Lipids in Health and Disease

JF - Lipids in Health and Disease

M1 - 75

ER -

The trans fatty acid elaidate affects the global DNA methylation profile of cultured cells and in vivo

Abstract

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