Manipulation of the Maternal Diet in Rat Pregnancy

Abstract

Animal studies of nutritional programming confirm the biological principle underpinning the “Barker Hypothesis”. Most studies have modelled the hypothesis in its simplest form, seeking to test the proposal that low birthweight predicts hypertension and, indeed, growth restricted offspring in many species do exhibit raised blood pressure as adults. A growing body of work with rodents has considered the programming effects of restricting single nutrients, including low protein feeding, high fat feeding and micronutrient restriction. Quite subtle shifts in the composition of the diet in pregnancy appear to produce potent effects, with hypertension, glucose intolerance, impaired immunity and reduced longevity noted with restriction of maternal protein, iron, sodium or calcium intakes. Although the nature and severity of the insults applied vary greatly between models, the general finding is that either balanced undernutrition or restriction of specific nutrients promotes metabolic and physiological disturbance and also relative adiposity in adult life. Intrauterine influences upon feeding, metabolism and the deposition of adipose tissue may well be mediated at the level of the hypothalamus. Microarray studies of the offspring of protein-restricted pregnant rats, which exhibit a preference for a high-fat food, indicate altered hypothalamic expression of a number of genes relating to signal transduction and homeostatic functions. The common outcomes of a range of nutrient manipulations in pregnancy suggest that a small number of common mechanisms may operate to reset the structure and long-term functions of most tissues. Timing and duration of the insult appears to be a more important determinant of long-term disease outcomes than the nature of the nutrient challenge.