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Open AccessArticle

Maternal Exposure to High-Fat Diet Induces Long-Term Derepressive Chromatin Marks in the Heart

1
Woman-Mother-Child Department, Division of Pediatrics, DOHaD Laboratory, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Rue du Bugnon 27, 1011 Lausanne, Switzerland
2
INSERM U1065, Centre Méditerranéen de Médecine Moléculaire (C3M), Team 5, 06204 Nice, France
*
Author to whom correspondence should be addressed.
BS and US contributed equally to this work.
Nutrients 2020, 12(1), 181; https://doi.org/10.3390/nu12010181
Received: 28 November 2019 / Revised: 30 December 2019 / Accepted: 7 January 2020 / Published: 9 January 2020
(This article belongs to the Special Issue Early Overnutrition and Long-Term Health Effects)
Heart diseases are a leading cause of death. While the link between early exposure to nutritional excess and heart disease risk is clear, the molecular mechanisms involved are poorly understood. In the developmental programming field, increasing evidence is pointing out the critical role of epigenetic mechanisms. Among them, polycomb repressive complex 2 (PRC2) and DNA methylation play a critical role in heart development and pathogenesis. In this context, we aimed at evaluating the role of these epigenetic marks in the long-term cardiac alterations induced by early dietary challenge. Using a model of rats exposed to maternal high-fat diet during gestation and lactation, we evaluated cardiac alterations at adulthood. Expression levels of PRC2 components, its histone marks di- and trimethylated histone H3 (H3K27me2/3), associated histone mark (ubiquitinated histone H2A, H2AK119ub1) and target genes were measured by Western blot. Global DNA methylation level and DNA methyl transferase 3B (DNMT3B) protein levels were measured. Maternal high-fat diet decreased H3K27me3, H2Ak119ub1 and DNA methylation levels, down-regulated the enhancer of zeste homolog 2 (EZH2), and DNMT3B expression. The levels of the target genes, isl lim homeobox 1 (Isl1), six homeobox 1 (Six1) and mads box transcription enhancer factor 2, polypeptide C (Mef2c), involved in cardiac pathogenesis were up regulated. Overall, our data suggest that the programming of cardiac alterations by maternal exposure to high-fat diet involves the derepression of pro-fibrotic and pro-hypertrophic genes through the induction of EZH2 and DNMT3B deficiency. View Full-Text
Keywords: heart; high-fat diet; development; polycomb repressive complex; DNA methylation heart; high-fat diet; development; polycomb repressive complex; DNA methylation
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Blin, G.; Liand, M.; Mauduit, C.; Chehade, H.; Benahmed, M.; Simeoni, U.; Siddeek, B. Maternal Exposure to High-Fat Diet Induces Long-Term Derepressive Chromatin Marks in the Heart. Nutrients 2020, 12, 181.

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