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Restricted fetal growth and the response to dietary cholesterol in the guinea pig
K L Kind1, P M Clifton, A I Katsman
1CSIRO Health Sciences and Nutrition, Adelaide, South Australia, 5000.
Insights
Maternal undernutrition during pregnancy permanently impacts cholesterol metabolism in male offspring. Lower birth weight due to poor prenatal nutrition leads to higher adult cholesterol levels, especially after consuming cholesterol.
Area of Science:
- Endocrinology
- Developmental Biology
- Nutritional Science
Background:
- Epidemiological studies link prenatal growth restriction to elevated adult plasma cholesterol.
- Prenatal growth perturbations may permanently disrupt cholesterol metabolism.
- The direct impact of prenatal nutrition on postnatal cholesterol homeostasis requires investigation.
Purpose of the Study:
- To investigate whether maternal undernutrition and resulting restricted prenatal growth alter postnatal cholesterol homeostasis in guinea pigs.
- To determine the long-term effects of prenatal nutritional status on adult cholesterol response to dietary cholesterol.
Main Methods:
- Adult male and female guinea pig offspring from mothers with ad libitum feeding or 85% ad libitum intake during pregnancy were studied.
- Offspring were fed a diet containing 0.25% cholesterol for 6 weeks.
- Plasma total cholesterol and low-density lipoprotein (LDL) cholesterol were measured before and after cholesterol feeding.
- Offspring were categorized by birth weight (above or below median) to assess the impact of size at birth.
Main Results:
- Maternal undernutrition reduced offspring birth weight by 13%.
- Male offspring of undernourished mothers exhibited higher plasma total cholesterol both before and after cholesterol feeding.
- In male offspring, low birth weight was associated with significantly higher plasma total and LDL cholesterol after cholesterol feeding compared to high birth weight.
- Female offspring showed no significant alterations in cholesterol response related to maternal nutrition or birth weight.
- Maternal undernutrition's effect on adult cholesterol was partly explained by altered prenatal growth.
Conclusions:
- Maternal undernutrition during pregnancy permanently alters postnatal cholesterol homeostasis in male guinea pigs.
- Reduced birth weight, a consequence of maternal undernutrition, is a key factor in the observed long-term changes in cholesterol metabolism.
- These findings highlight the critical role of prenatal nutrition in establishing lifelong metabolic health, particularly concerning cholesterol regulation in males.
Abstract:
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.