Abstract

BackgroundThe 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.MethodsBased 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.ResultsEA 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.ConclusionWe 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-016-0243-2) contains supplementary material, which is available to authorized users.

Highlights

  • The deleterious effects of dietary trans fatty acids on human health are well documented

  • Effects of elaidic acid (EA) and oleic acid (OA) on global DNA methylation We first explored the effects of EA and OA on global DNA methylation, i.e. total 5mdC content calculated by an HPLC-based technique - in THP-1 monocytes

  • EA induced a biphasic effect on global DNA methylation, i.e. a hypermethylation in the 1–50 μM dose range corresponding to a 5.2 % increase in 5mdC levels, followed by a sharp hypomethylation up to the 200 μM dose (Fig. 1)

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Summary

Introduction

The deleterious effects of dietary trans fatty acids (tFAs) on human health are well documented. Fatty acid (FA) trans isomers (tFAs) produced by fat hydrogenation in the food processing industry have been extensively linked to pathologies such as cardiovascular disease, diabetes and obesity [1]. We asked whether EA modifies the DNA methylome and the transcriptome and whether such effects are distinct from the ones elicited by its cis isomer oleic acid (OA) in human THP-1 monocytes. The rationale for using the THP-1 cell line as model is that it has been exploited to study the effects of lipoproteins and FAs on the DNA methylome ([3, 11] and our group’s unpublished data). In order to explore possible epigenetic long-term effects, we assessed whether EA shapes the DNA methylome in utero or during lactation in a mouse model. We discuss the results in the light of the current knowledge of FAs and disease risk

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