Maternal high fat diet induces early cardiac hypertrophy and alters cardiac metabolism in Sprague Dawley rat offspring

Jong, Kirstie A. De; Barrand, Sanna; Wood-Bradley, Ryan J; Almeida, Douglas Lopes; Czeczor, Juliane K.; Lopaschuk, Gary D.; Armitage, James A.; McGee, Sean L.

doi:10.1016/j.numecd.2018.02.019

Cited by 15 publications

(11 citation statements)

References 41 publications

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“…Maternal obesity and high-fat diet have been associated with increased risk for heart diseases, notably through the induction of cardiac remodeling. Indeed, maternal exposure to high-fat diet induces cardiac hypertrophy and fibrosis that are observed early during development (at PND1 and PND10) 6,29 . Our current study showed that maternal exposure to high-fat diet induced long-term histological and molecular changes in the heart prior to the onset of overt obesity.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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“…Aside methylation and ubiquitination, histone acetylation is one of the best characterized modifications and relies on the activity of histone acetyltransferases (HATs) [40] and histone deacetylases (HDACs). In the context of maternal exposure to high-fat diet, increased signaling involving the class IIa HDAC has been reported at postnatal day 10 in the heart [41]. The involvement of HATs and HDACs in cardiac hypertrophy and fibrosis is explained by their ability to regulate histone acetylation at the promoter region of Gata4 and Mef2c and to associate with these transcription factors [42].…”

Section: Discussionmentioning

confidence: 99%

“…The involvement of HATs and HDACs in cardiac hypertrophy and fibrosis is explained by their ability to regulate histone acetylation at the promoter region of Gata4 and Mef2c and to associate with these transcription factors [42]. By this way, HATs and HDACs have been shown to regulate the expression of genes implicated in the control of stress-induced growth of the adult heart such as Anp and brain natriuretic peptide (Bnp) [41,43] as well as genes involved in fatty acid metabolism [41]. Importantly, the nutrition-dependent changes in DNA methylation and in histone marks can be gene specific.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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“…Similarly, lipid and fatty acid accumulation are strictly correlated with CVD predisposition [1,2]. Maternal HFD has also been shown to reprogram cardiac metabolism and induces cardiac hypertrophy [150,151] and myocardial cell fat deposition [152]. Interestingly, Watkins et al found in a murine model in which mothers had a low protein diet during the pre-implantation period (days 0 to 3.5 of embryonic development), that the offspring showed arterial hypertension during postnatal life [153], as do offspring exposed to maternal low protein diet during the whole pregnancy [154,155].…”

Section: Nutritional Effects On Cardiomyocytes Functionmentioning

confidence: 99%

Environmental Alterations during Embryonic Development: Studying the Impact of Stressors on Pluripotent Stem Cell-Derived Cardiomyocytes

Lamberto

Peral-Sanchez

Muenthaisong

et al. 2021

Genes

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Non-communicable diseases (NCDs) sauch as diabetes, obesity and cardiovascular diseases are rising rapidly in all countries world-wide. Environmental maternal factors (e.g., diet, oxidative stress, drugs and many others), maternal illnesses and other stressors can predispose the newborn to develop diseases during different stages of life. The connection between environmental factors and NCDs was formulated by David Barker and colleagues as the Developmental Origins of Health and Disease (DOHaD) hypothesis. In this review, we describe the DOHaD concept and the effects of several environmental stressors on the health of the progeny, providing both animal and human evidence. We focus on cardiovascular diseases which represent the leading cause of death worldwide. The purpose of this review is to discuss how in vitro studies with pluripotent stem cells (PSCs), such as embryonic and induced pluripotent stem cells (ESC, iPSC), can underpin the research on non-genetic heart conditions. The PSCs could provide a tool to recapitulate aspects of embryonic development “in a dish”, studying the effects of environmental exposure during cardiomyocyte (CM) differentiation and maturation, establishing a link to molecular mechanism and epigenetics.

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Maternal high fat diet induces early cardiac hypertrophy and alters cardiac metabolism in Sprague Dawley rat offspring

Cited by 15 publications

References 41 publications

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

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

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

Environmental Alterations during Embryonic Development: Studying the Impact of Stressors on Pluripotent Stem Cell-Derived Cardiomyocytes

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