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Gene expression profiling and TF occupancy upon treatment with the FXR agonist obeticholic acid

ABSTRACT: The farnesoid X receptor (FXR) is a nuclear receptor activated by bile acids and regulates bile acid metabolism, glucose and cholesterol homeostasis. From mouse studies we know that the novel FXR agonist obeticholic acid (OCA) regulates expression of many genes in the liver, but there is currently no data on the effects of OCA on human liver gene expression. This is especially relevant since the novel FXR agonist OCA is currently tested in clinical trials for the treatment of several diseases, such as nonalcoholic steatohepatitis (NASH), nonalcoholic fatty liver disease (NAFLD) and Type 2 Diabetes. In this study we investigate the effect of OCA treatment on gene expression profiles and localization of FXR to the genome in relevant liver samples. ChIP-Seq for FXR in Liver tissue from 2 male mice treated with OCA/INT-747 (10mg/kg/day) and 2 male mice treated with vehicle (1% methyl cellulose).

ORGANISM(S): Mus musculus

SUBMITTER: Jose Miguel Ramos Pittol 

PROVIDER: E-GEOD-73624 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression profiling in human precision cut liver slices in response to the FXR agonist obeticholic acid.

Ijssennagger Noortje N   Janssen Aafke W F AWF   Milona Alexandra A   Ramos Pittol José M JM   Hollman Danielle A A DAA   Mokry Michal M   Betzel Bark B   Berends Frits J FJ   Janssen Ignace M IM   van Mil Saskia W C SWC   Kersten Sander S  

Journal of hepatology 20160123 5

<h4>Background & aims</h4>The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA alters hepatic expression of many genes. However, no data are available on the effects of OCA in the human liver. Here we generated gene expression profi  ...[more]

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