The sources of rat biliary cholesterol and bile acid.

Abstract

The precursor sources of bile acid and bile neutral sterol were evaluated in the rat using Triparanol to inhibit the terminal reduction in the synthesis of cholesterol. During the initial period of Triparanol administration, the accumulation of hepatic desmosterol acts to segregate relatively newly synthetic hepatic sterol from the bulk of the equilibrated sterol mass. Biliary excretion of newly synthetic sterol can then be determined in acute studies, assuming no great differences between desmosterol and cholesterol as precursors of biliary neutral sterol or bile acid. It has been determined in this model that newly synthetic sterol comprises a mean of about 28% of the total biliary neutral sterol output. This fraction fell when hepatic cholesterogenesis was suppressed by prior cholesterol feeding. By using this approach in conjunction with the administration of labeled mevalonate to a renal pedicle-ligated rat, it was possible to calculate the amount of bile acid produced from either newly synthesized sterol or the equilibrated sterol pool. It has been estimated that the bulk of bile acid synthesis arises from this equilibrated source when these determinations were made within two hours of creating the fistula. With more prolonged fistula times, more of the bile acid originated from the newly synthesized sterol.