Review article: effect of bile salt pool composition on hepatic and biliary functions

The enterohepatic recirculation of bile salts exerts important regulatory e ffects on many hepatic, biliary and intestinal functions; such regulation i s likely to depend, to a large extent, on the physical-chemical property of hydrophobicity of the recirculating pool. The present review summarizes th e main experimental evidence carried out by our research group over the pas t two decades, in the attempt to investigate systematically the relationshi ps between structural properties and biological effects of bile acids in hu mans. Hydrophobic bile acids (chenodeoxycholic acid, deoxycholic acid), but not hydrophilic acids (ursodeoxycholic acid), significantly suppressed hep atic activity of HMG-CoA reductase, the limiting step of cholesterol synthe sis, and in vivo cholesterol 7 alpha-hydroxylation, the limiting step of bi le acid synthesis. The output of biliary cholesterol and phospholipid was a lso directly related to the hydrophobicity of the bile acid pool. Finally, treatment with chenodeoxycholic acid, but not with ursodeoxycholic acid, si gnificantly decreased gallbladder emptying rates. When turning to the in vi tro model of HepG2 cells, hydrophobic bile acids were found to induce great er cytotoxic and pro-apoptotic effects. From this series of studies, we con clude that the regulatory effects of bile acids on the liver and biliary tr act are largely dependent on the hydrophobic-hydrophilic balance of the rec irculating bile acid pool.