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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-12

AUTHORS

Benazir Siddeek, Claire Mauduit, Hassib Chehade, Guillaume Blin, Marjorie Liand, Mariapia Chindamo, Mohamed Benahmed, Umberto Simeoni

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. More... »

PAGES

71

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41420-019-0153-y

DOI

http://dx.doi.org/10.1038/s41420-019-0153-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112472780

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30854230


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41420-019-0153-y'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41420-019-0153-y'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41420-019-0153-y'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41420-019-0153-y'


 

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