Maternal resveratrol supplementation and its effects on cardiac hypertrophy, mitochondrial metabolism, and calcium flux in isolated fetal cardiomyocytes
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Abstract
Gestational diabetes mellitus (GDM) is a condition that manifests in pregnancy that is characterized by insulin resistance, glucose intolerance, and hyperglycemia. Medications have shown effectiveness but have associated risk of adverse pregnancy outcomes. Our previous studies in rats found cardiomyocytes of GDM-offspring exhibit hypertrophy, mitochondrial dysfunction, and impaired calcium flux. We hypothesize that administration of resveratrol (RESV) to maternal GDM diet will mitigate mitochondrial dysfunction, cardiac hypertrophy and improve calcium flux in GDM-offspring. A diet-induced model was implemented on female Sprague-Dawley rats six weeks before mating to induce GDM. A subgroup of GDM dams were switched to a diet containing RESV. Fetal echocardiography was performed to assess cardiac structure. Measurements of mitochondrial respiration and calcium flux were performed using the Agilent-Seahorse XF 24 and Cytation 5. Maternal RESV supplementation improved mitochondrial respiration and improved calcium flux upon angiotensin II stimulation. Importantly, maternal RESV supplementation attenuated GDM-induced cardiac hypertrophy in GDM-offspring.