The influence of dietary cholesterol and fat on the homeostasis of cholesterol metabolism in early life in the rat

Abstract

Evidence has accumulated suggesting that exposure to dietary cholesterol during early development stages activates biochemical mechanisms that regulate cholesterol homeostasis in adult life. Pregnant Sprague-Dawley rats were fed control or 1% cholesterol [high cholesterol-high fat (HC-HF)] liquid diet during gestation, and with the same diet, offsprings were challenged at maturity. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase activity declined by 76%, and cholesterol 7 α-hydroxylase activity increased by 200%. Microsomal and serum cholesterol accumulation also increased significantly. Exposure to HC-HF diet during suckling and continued exposure with the same diet postweaning resulted in 52% decline in 3-hydroxy-3-methylglutaryl coenzyme A reductase and 280% increase in 7α-hydroxylase activity. Serum cholesterol levels is not affected although microsomal cholesterol accumulation and the ratio of hepatic to serum cholesterol increased significantly in the experimental group when compared to the nonchallenged group. Rats exposed to HC-HF diet during lactation alone or during gestation and lactation and then challenged demonstrated enzymatic changes of similar magnitude. Serum and microsomal cholesterol levels also increased significantly by 126 and 150%, respectively. The activity of the HMG-CoA reductase system appears to be more sensitive to modulation by diet during gestation than during lactation. However, 7α-hydroxylase activity is susceptible to dietary manipulation with HC-HF diet only during lactation. Low 3-hydroxy-3-methylglutaryl coenzyme A reductase and high cholesterol 7α-hydroxylase activities in animals exposed to high cholesterol-high fat diet during gestation and challenged with the same diet at maturity supports the hypothesis that diet during early life influences the regulation of cholesterol homeostasis in adults. Furthermore, our results also suggest that significant alteration of 7α-hydroxylase activity during lactation, but not during gestation, may be due to late development of the bile acid-metabolizing system during gestation in rats as is known to occur in humans.