Maternal Choline Intake Programs Hypothalamic Energy Regulation and Later-Life Phenotype of Male Wistar Rat Offspring

Scope: High-folic-acid diets during pregnancy result in obesity in the offspring, associated with altered DNA-methylation of hypothalamic food intake neurons. Like folic acid, the methyl-donor choline modulates foetal brain development, but its long-term programing effects on energy regulation remain undefined. This study aims to describe the effect of choline intake during pregnancy on offspring phenotype and hypothalamic energy-regulatory mechanisms. Methods and results: Wistar rat dams are fed an AIN-93G diet with recommended choline (RC, 1 g kg(-1) diet), low choline (LC, 0.5-fold), or high choline (HC, 2.5-fold) during pregnancy. Male pups are terminated at birth and 17 weeks post-weaning. Brain 1-carbon metabolites, body weight, food intake, energy expenditure, plasma hormones, and protein expression of hypothalamic neuropeptides are measured. HC pups have higher expression of the orexigenic neuropeptide-Y neurons at birth, consistent with higher cumulative food intake and body weight gain post-weaning compared to RC and LC offspring. LC pups have lower leptin receptor expression at birth and lower energy expenditure and activity during adulthood. Conclusion: Choline content of diets that are consumed by rats during pregnancy affects the later-life phenotype of offspring, associated with altered in utero programing of hypothalamic food intake regulation.