Restricted fetal growth and the response to dietary cholesterol in the guinea pig

Epidemiological studies suggest that retarded growth before birth is associated with increased plasma total and low-density lipoprotein (LDL) cholesterol concentrations in adult life. Thus perturbations of prenatal growth may permanently alter cholesterol metabolism. To determine directly whether restriction of prenatal nutrition and growth alters postnatal cholesterol homeostasis, the plasma cholesterol response to cholesterol feeding (0.25% cholesterol) was examined in adult guinea pig offspring of ad libitum-fed or moderately undernourished mothers. Maternal undernutrition (85% ad libitum intake throughout pregnancy) reduced birth weight (-13%). Plasma total cholesterol was higher prior to and following 6 wk cholesterol feeding in male offspring of undernourished mothers compared with male offspring of ad libitum-fed mothers (P < 0.05). The influence of birth weight on cholesterol metabolism was examined by dividing the offspring into those whose birth weight was above (high) or below (low) the median birth weight. Plasma total cholesterol concentrations prior to cholesterol feeding did not differ with size at birth, but plasma total and LDL cholesterol were 31 and 34% higher, respectively, following cholesterol feeding in low- compared with high-birth weight males (P < 0.02). The response to cholesterol feeding in female offspring was not altered by variable maternal nutrition or size at birth. Covariate analysis showed that the effect of maternal undernutrition on adult cholesterol metabolism could be partly accounted for by alterations in prenatal growth. In conclusion, maternal undernutrition and small size at birth permanently alter postnatal cholesterol homeostasis in the male guinea pig.