Effect of neonatal modulation of cholesterol homeostasis on subsequent response to cholesterol challenge in adult guinea pig.

Experiments were designed to study whether or not the mechanism of handling dietary cholesterol in adulthood can be modulated by the manipulation of cholesterol homeostasis during neonatal period. The effects of enhancing cholesterol degradation (cholestyramine feeding), high dietary cholesterol intake, and early weaning during neonatal period of guinea pigs on their subsequent plasma cholesterol levels and the response to dietary cholesterol challenged in adulthood were investigated. Pretreatment of neonatal guinea pigs with cholestyramine resulted in (a) a lower plasma cholesterol level, (b) an increased excretion rate of fecal bile acids and total steroids, (c) an expanded bile acid pool, (d) an increased activity of cholesterol 7 alpha-hydroxylase, and (e) no change in the hepatic 3-hydroxy-3-methylglutaryl coenzyme A (CoA) reductase activity when challenged with cholesterol in adulthood. Cholesterol pretreatment during neonatal period resulted in (a) no alteration in the plasma cholesterol level, (b) no alteration in the fecal excretion of steroids, or (c) no alteration in the cholesterol 7 alpha-hydroxylase activity when they were challenged with a high cholesterol diet. Early weaning did not influence the fecal excretion of steroids or cholesterol 7 alpha-hydroxylase activity but resulted in a slight decrease in the hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity when they were challenged with a high cholesterol diet. These results suggest that stimulation of cholesterol catabolism rather than cholesterol feeding or early weaning during neonatal period can influence the response to dietary cholesterol challenge in adulthood.