Prenatal programming in an obese swine model: sex-related effects of maternal energy restriction on morphology, metabolism and hypothalamic gene expression

Maternal energy restriction during pregnancy predisposes to metabolic alterations in the offspring. The present study was designed to evaluate phenotypic and metabolic consequences following maternal undernutrition in an obese pig model and to define the potential role of hypothalamic gene expression in programming effects. Iberian sows were fed a control or a 50% restricted diet for the last two-thirds of gestation. Newborns were assessed for body and organ weights, hormonal and metabolic status, and hypothalamic expression of genes implicated in energy homeostasis, glucocorticoid function and methylation. Weight and adiposity were measured in adult littermates. Newborns of the restricted sows were lighter (P<0.01), but brain growth was spared. The plasma concentration of TAG was lower in the restricted newborns than in the control newborns of both the sexes (P<0.01), while the concentration of cortisol was higher in females born to the restricted sows (P<0.04), reflecting a situation of metabolic stress by nutrient insufficiency. A lower hypothalamic expression of anorexigenic peptides (LEPR and POMC, P<0.01 and P<0.04, respectively) was observed in females born to the restricted sows, but no effect was observed in the males. The expression of HSD11B1 gene was down-regulated in the restricted animals (P<0.05), suggesting an adaptive mechanism for reducing the harmful effects of elevated concentrations of cortisol. At 4 and 7 months of age, the restricted females were heavier and fatter than the controls (P<0.01). Maternal feed restriction induces asymmetrical growth retardation and metabolic alterations in the offspring. Differences in gene expression at birth and higher growth and adiposity in adulthood suggest a female-specific programming effect for a positive energy balance, possibly due to overexposure to endogenous stress-induced glucocorticoids.