FXR agonist GW4064 improves the liver and intestinal pathology and alters bile acid metabolism in rats undergoing small intestinal resection.

FXR agonist GW4064 improves the liver and intestinal pathology and alters bile acid metabolism in rats undergoing small intestinal resection. Am J Physiol Gastrointest Liver Physiol. 2019 Mar 28;: Authors: Cao Y, Xiao Y, Zhou K, Yan J, Wang P, Yan W, Cai W Abstract Mortality associated with liver disease was observed in patients with short bowel syndrome (SBS); however, its mechanism remains unclear. Bile acid (BA) dysmetabolism may be one of the putative mechanisms, and farnesoid X receptor (FXR) is the key regulator of BA synthesis. Here, we showed that in a rat model of small bowel resection associated with liver disease (SBR-ALD), BA composition of hepatic tissues reflected a larger proportion of primary and secondary unconjugated BAs, and those of colon contents and serum showed an increased ratio of secondary unconjugated BAs. Both hepatic and intestinal regulation of BA synthesis was characterized by a blunted hepatic FXR activation response. Gene expression of the key enzymes in BA synthesis was activated. After intervention with FXR agonist GW4064, both liver histology and serum transaminase activity were improved, which demonstrated the attenuation of SBR-ALD. BA compositions of hepatic tissue, colon contents, and serum were recovered and were closer to those of the sham group. Expression levels of hepatic FXR and its target genes were activated. The study showed that FXR agonist GW4064 could balance BA dysmetabolism to all...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research