Premature weaning-induced changes of cholesterol metabolism in guinea pigs

Premature weaning in animals causes higher serum cholesterol levels and a relative inability to handle cholesterol challenge in adult life. The mechanisms responsible for these delayed effects of premature weaning are not clear. The aims of this investigation were to 1) determine the effect of premature weaning on the activity of hepatic cholesterol 7 alpha-hydroxylase and plasma cholesterol changes and 2) determine whether addition of cholesterol to the diet will restore premature weaning-induced changes. Premature weaning did not prevent the phenomenon of neonatal hypercholesterolemia noted in day 5 of normally weaned guinea pigs. At day 10, prematurely weaned animals had lower serum cholesterol when compared with normally weaned animals. Premature weaning caused (without or with cholesterol in diet) a significant decrease in the hepatic activity of cholesterol 7 alpha-hydroxylase, and this difference persisted (after 1 mo) when fed the stock diet. These studies demonstrate 1) premature weaning on day 2 does not prevent neonatal hypercholesterolemia on day 5, 2) premature weaning causes a decrease in hepatic cholesterol 7 alpha-hydroxylase activity that persists into adult life, and 3) dietary cholesterol intake in early life is unable to negate premature weaning-induced changes.