Comment

Bile acids (BA) play an important role in human physiology.1 As amphipathic water soluble end products of cholesterol metabolism, they participate in body cholesterol disposal as well as generation of bile flow and biliary lipid secretion. However, in spite of being key endobiotics, BA are intrinsically toxic for cells mainly because of their inherent detergent and membrane disruptive properties. In fact, BA induced hepatotoxicity has been implicated in the pathogenesis and perpetuation of liver injury in cholestatic liver diseases.2 Therefore, it is not surprising that intracellular BA levels are tightly maintained within a narrow concentration range3 as too much leads to hepatotoxicity while too little can lead to significant impairments in bile flow and luminal fat digestion. How the liver orchestrates the regulation of intracellular BA concentrations appears to be through transcriptional regulation of genes involved in both BA biosynthesis and transport. The recent cloning and identification of major enzymes and transport proteins involved in the synthesis and enterohepatic circulation of BA have provided insight into how this regulation takes place.4 ,5 Available data suggest that BA may indeed participate in transcriptional activation or repression of several genes involved in the conversion of cholesterol into BA as well as hepatic transport.6 Relevant examples are BA mediated feedback inhibition of cholesterol 7alpha-hydroxylase (CYP7A1),7 the rate limiting enzyme in BA biosynthesis, and the sinusoidal Na(+)/bile acid cotransporter (Ntcp), the main uptake system for BA …