Abstract

Maternal choline intakes are below recommendations, potentially impairing the child’s later-life metabolic health. This study aims to elucidate the interaction between the choline content of the gestational diet (GD) and fat content of the post-weaning diet (PWD) on metabolic phenotype of male Wistar rats. Pregnant Wistar rats were fed a standard rodent diet (AIN-93G) with either recommended choline (RC, 1 g/kg diet choline bitartrate) or high choline (HC, 2.5-fold). Male pups were weaned to either a normal (16%) fat (NF) or a high (45%) fat (HF) diet for 17 weeks. Body weight, visceral adiposity, food intake, energy expenditure, plasma hormones, triglycerides, and hepatic fatty acids were measured. HC-HF offspring had 7% lower body weight but not food intake, and lower adiposity, plasma triglycerides, and insulin resistance compared to RC-HF. They also had increased hepatic n-3 fatty acids and a reduced n-6/n-3 and C 18:1 n-9/C18:0 ratios. In contrast, HC-NF offspring had 6–8% higher cumulative food intake and body weight, as well as increased leptin and elevated hepatic C16:1 n-7/C16:0 ratio compared to RC-NF. Therefore, gestational choline supplementation associated with improved long-term regulation of several biomarkers of the metabolic syndrome in male Wistar rat offspring fed a HF, but not a NF, PWD.

Highlights

  • Maternal nutritional imbalances during pregnancy may alter metabolic adaptive responses in the fetus in utero, resulting in long-term metabolic changes to prepare the newborn for the post-natal environment [1]

  • Male pups born from dams fed an high choline (HC) diet during pregnancy had significantly lower plasma leptin concentration compared to recommended choline (RC) group (Table S3)

  • When stratified by post-weaning diet (PWD), HC-normal fat (NF) offspring had 8% higher food intake compared to RC-NF (p < 0.01), but cumulative food intake was not different between RC-high fat (HF) and HC-HF offspring

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Summary

Introduction

Maternal nutritional imbalances during pregnancy may alter metabolic adaptive responses in the fetus in utero, resulting in long-term metabolic changes to prepare the newborn for the post-natal environment [1]. One possible mechanism facilitating these early-life adaptations involve DNA-methylation-dependent epigenetic modifications affecting gene expression associated with the regulation of energy balance and metabolism [2,3]. Despite being an essential nutrient during gestation, epidemiological studies show that less than 10% of North American pregnant women meet the adequate dietary intake requirements for choline [5]. It is absent from most multivitamin prenatal supplements [6], raising concern of possible adverse health effects. We recently showed that a high (2.5-fold) choline diet consumed by Wistar rats during pregnancy programs long-term hypothalamic energy regulation in their offspring [7]. Higher expression of the orexigenic neuropeptide-Y neurons in newborn pups reflected their later-life increase in cumulative food intake and body weight gain when fed a normal fat (NF, 16% of calories) post-weaning diet (PWD) [7]

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