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Metabolic maturation of neonatal hearts driven by γ-linolenic acid in maternal milk [ATAC-seq]

ABSTRACT: The goal of this study was to compare the epigenetic landscape of perinatal hearts of cardiomyocyte-specific RXRab-deficient (edKO) and WT mice, to identify differential chromatin dynamics that are controlled by TF RXRa and RXRb.

ORGANISM(S): Mus musculus

PROVIDER: GSE188997 | GEO | 2023/02/15

REPOSITORIES: GEO

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Metabolic maturation of neonatal hearts driven by γ-linolenic acid in maternal milk [H3K27ac ChIP-seq]

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Metabolic maturation of neonatal hearts driven by γ-linolenic acid in maternal milk

Project description:Birth is the first metabolic challenge that cardiomyocytes need to overcome as they reshape their fuel preference from glucose to fatty acids (FA) to optimize energy production in postnatal life. This adaptation is partly triggered by drastic post-partum environmental changes, yet the molecular players responsible for orchestrating cardiomyocyte maturation remain unknown. Here, we discover that maternal metabolite γ-linolenic acid (GLA) support this transition. Specifically, colostrum GLA acts as an agonist for Retinoid X Receptors (RXR), a family of ligand-activated transcription factors expressed from embryonic life in cardiomyocytes. Mice lacking RXR in embryonic cardiomyocytes showed an aberrant chromatin landscape that prevented the induction of RXR-dependent FA metabolism genes (mtFAH signature). This results in a defective metabolic transition with blunted mitochondrial lipid-derived energy production and enhanced glucose consumption, which ultimately leads to perinatal lethal cardiac dysfunction. In vitro GLA supplementation in cardiomyocytes induced the expression of mtFAH signature in a RXR-dependent manner. Altogether, our study uncovers GLA/RXR axis as the fundamental mechanism by which maternal physiology commands metabolic functioning in perinatal hearts. This SuperSeries is composed of the SubSeries listed below.

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