Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis.

Details

Serval ID
serval:BIB_E53CF748D8D7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Long-term impact of maternal high-fat diet on offspring cardiac health: role of micro-RNA biogenesis.
Journal
Cell death discovery
Author(s)
Siddeek B., Mauduit C., Chehade H., Blin G., Liand M., Chindamo M., Benahmed M., Simeoni U.
ISSN
2058-7716 (Print)
ISSN-L
2058-7716
Publication state
Published
Issued date
2019
Peer-reviewed
Oui
Volume
5
Pages
71
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Heart failure is a worldwide leading cause of death. Diet and obesity are particularly of high concern in heart disease etiology. Gravely, altered nutrition during developmental windows of vulnerability can have long-term impact on heart health; however, the underlying mechanisms are poorly understood. In the understanding of the initiation of chronic diseases related to developmental exposure to environmental challenges, deregulations in epigenetic mechanisms including micro-RNAs have been proposed as key events. In this context, we aimed at delineating the role of micro-RNAs in the programming of cardiac alterations induced by early developmental exposure to nutritional imbalance. To reach our aim, we developed a human relevant model of developmental exposure to nutritional imbalance by maternally exposing rat to high-fat diet during gestation and lactation. In this model, offspring exposed to maternal high-fat diet developed cardiac hypertrophy and increased extracellular matrix depot compared to those exposed to chow diet. Microarray approach performed on cardiac tissue allowed the identification of a micro-RNA subset which was down-regulated in high-fat diet-exposed animals and which were predicted to regulate transforming growth factor-beta (TGFβ)-mediated remodeling. As indicated by in vitro approaches and gene expression measurement in the heart of our animals, decrease in DiGeorge critical region 8 (DGCR8) expression, involved in micro-RNA biogenesis, seems to be a critical point in the alterations of the micro-RNA profile and the TGFβ-mediated remodeling induced by maternal exposure to high-fat diet. Finally, increasing DGCR8 activity and/or expression through hemin treatment in vitro revealed its potential in the rescue of the pro-fibrotic phenotype in cardiomyocytes driven by DGCR8 decrease. These findings suggest that cardiac alterations induced by maternal exposure to high-fat diet is related to abnormalities in TGFβ pathway and associated with down-regulated micro-RNA processing. Our study highlighted DGCR8 as a potential therapeutic target for heart diseases related to early exposure to dietary challenge.
Pubmed
Web of science
Open Access
Yes
Create date
08/04/2019 16:39
Last modification date
20/08/2019 16:08
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