Executive Summary

Suppression of Hepatic XBP1s Decreases the Bile Salt Pool Cholestatic liver diseases are a highly prevalent group of liver diseases that result in the toxic buildup of bile salts in the liver. Bile salts are the main constituent of bile, which has a number of functions, including breaking down fat, within the digestive system. A gene, XBP1, has been shown to not only regulate the Unfolded Protein Response pathway (UPR), but also appears to regulate liver bile salt production. The UPR protects against cellular stress when proteins are incorrectly folded in a cell. This study uses High Pressure Liquid Chromatography (HPLC), to investigate the consequences of a liver-specific XBP1 gene deletion on the bile salt concentrations and the hydrophobicity of the bile salts. Hydrophobic bile salts can cause liver injury, while hydrophilic bile salts are more beneficial to the liver. Mice bile salts were extracted from the liver, gallbladder, and the intestinal tract. After purification of the bile salts from the bile, HPLC was used to determine the total amount of bile salts. We demonstrate that the experimental liverspecific XBP1 deleted mice have a smaller bile salt pool compared to the control mice. Furthermore, we demonstrate that the concentration of hydrophobic bile salts is significantly lower in the experimental mice. By proving that the deletion of the XBP1 transcription gene in liver cells changes the bile salt concentration, we believe that the findings can be applicable in developing affective medicine to treat these cholestatic liver diseases.