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

Epidemiological studies suggest that retarded growth before birth is associ ated with increased plasma total and low-density lipoprotein (LDL) choleste rol concentrations in adult life. Thus perturbations of prenatal growth may permanently alter cholesterol metabolism. To determine directly whether re striction of prenatal nutrition and growth alters postnatal cholesterol hom eostasis, the plasma cholesterol response to cholesterol feeding (0.25% cho lesterol) was examined in adult guinea pig offspring of ad libitum-fed or m oderately undernourished mothers. Maternal undernutrition (85% ad libitum i ntake throughout pregnancy) reduced birth weight (-13%). Plasma total chole sterol was higher prior to and following 6 wk cholesterol feeding in male o ffspring of undernourished mothers compared with male offspring of ad libit um-fed mothers (P < 0.05). The influence of birth weight on cholesterol met abolism was examined by dividing the offspring into those whose birth weigh t was above thigh) or below (low) the median birth weight. Plasma total cho lesterol concentrations prior to cholesterol feeding did not differ with si ze at birth, but plasma total and LDL cholesterol were 31 and 34% higher, r espectively, following cholesterol feeding in low-compared with high-birth weight males (P < 0.02). The response to cholesterol feeding in female offs pring was not altered by variable maternal nutrition or size at birth. Cova riate analysis showed that the effect of maternal undernutrition on adult c holesterol metabolism could be partly accounted for by alterations in prena tal growth. In conclusion, maternal. undernutrition and small size at birth permanently alter postnatal cholesterol homeostasis in the male guinea pig .