Mechanism of Lithogenic Bile Production: Studies in the Hamster Fed an Essential Fatty Acid-Deficient Diet

Abstract

The essential fatty acid-deficient (EFAD) hamster forms lithogenic hepatic bile and gallstones of high cholesterol content. Measurements of bile acid kinetics and biliary lipid secretion have been performed in this animal model to determine if bile becomes lithogenic as a result of an absolute increase in cholesterol or as a consequence of a primary decrease in cholesterol-solubilizing lipids. EFAD feeding prolonged the turnover, increased reabsorption, and decreased synthesis of cholic acid. The pool size of cholate was, however, the same as in chow-fed control animals both preceding and after gallstone development. Biliary secretion rates were determined in nonfasted animals from the first 30-min bile collection after common duct cannulation. EFAD feeding resulted in no decrease in total bile salt or phospholipid output. In contrast, biliary cholesterol secretion in EFAD-fed hamsters was 2 to 3 times increased over control animals, and was significantly elevated prior to stone development. In EFAD hamsters, cystic duct ligation to exclude the gallbladder from the enterohepatic circulation produced an even greater elevation of cholesterol secretion, but did not influence the secretion rate of bile salt or phospholipid. In the EFAD hamster increased biliary cholesterol secretion was not associated with an increase in serum, liver, or whole carcass cholesterol levels. Thus, the production of bile of lithogenic composition in the EFAD hamster is clearly a consequence of selective enhancement of biliary cholesterol secretion, not eliminated by gallbladder exclusion, and not associated with a generalized increase in body cholesterol levels.