scholarly journals The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid

2014 ◽  
Vol 41 (1) ◽  
pp. 54-64 ◽  
Author(s):  
J. R. F. Walters ◽  
I. M. Johnston ◽  
J. D. Nolan ◽  
C. Vassie ◽  
M. E. Pruzanski ◽  
...  
Keyword(s):  
Bile Acid ◽  
Receptor Agonist ◽  
Farnesoid X Receptor ◽  
Obeticholic Acid

scholarly journals Tu1262 Obeticholic Acid, a Farnesoid X Receptor Agonist, Reduces Bile Acid Synthesis in Patients With Primary Bile Acid Diarrhea

2014 ◽  
Vol 146 (5) ◽  
pp. S-797 ◽  
Author(s):  
Claire Vassie ◽  
Jonathan D. Nolan ◽  
Ian M. Johnston ◽  
David Shapiro ◽  
Julian R. Walters
Keyword(s):  
Bile Acid ◽  
Receptor Agonist ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Farnesoid X Receptor ◽  
Obeticholic Acid ◽  
Primary Bile Acid

scholarly journals Obeticholic acid, a selective farnesoid X receptor agonist, regulates bile acid homeostasis in sandwich-cultured human hepatocytes

2017 ◽  
Vol 5 (4) ◽  
pp. e00329 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Jonathan P. Jackson ◽  
Robert L. St. Claire ◽  
Kimberly Freeman ◽  
Kenneth R. Brouwer ◽  
...  
Keyword(s):  
Bile Acid ◽  
Receptor Agonist ◽  
Human Hepatocytes ◽  
Farnesoid X Receptor ◽  
Obeticholic Acid

Tu1263 The Effects of Obeticholic Acid, a Farnesoid X Receptor Agonist, in Patients With Chronic Diarrhea Secondary to Crohn's Ileal Disease

2014 ◽  
Vol 146 (5) ◽  
pp. S-797
Author(s):  
Jonathan D. Nolan ◽  
Claire Vassie ◽  
Ian M. Johnston ◽  
Tracy Dew ◽  
David Shapiro ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Chronic Diarrhea ◽  
Farnesoid X Receptor ◽  
Obeticholic Acid ◽  
Ileal Disease

scholarly journals Obeticholic Acid Protects Against Cholestatic Liver Injury Induced by Lithocholic Acid via Inhibiting Exogenous Cell Apoptosis

2021 ◽  
Author(s):  
Yangping Zhu ◽  
Changling Wang ◽  
Jingyi Yu ◽  
Yingying Miao ◽  
Yuanyuan Chai ◽  
...  
Keyword(s):  
Bile Acid ◽  
Liver Injury ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Lithocholic Acid ◽  
Farnesoid X Receptor ◽  
Multi Drug Resistance ◽  
Caspase 8 ◽  
Obeticholic Acid ◽  
Cholestatic Liver Injury

Abstract Background: Lithocholic acid (LCA) is one kind of endogenous bile acids which is a typical index in primary biliary cholangitis (PBC). It could cause severe cholestatic liver injury in rodents. Obeticholic acid (OCA) is a major treatment for PBC. However, its effect and mechanism in LCA-induced liver injury was still unclear beside of bile acid regulation. This study aims to evaluate the hepatoprotective effect and mechanism of OCA against LCA-induced cholestatic liver injury. Results: LCA-induced upregulations of ALT, AST, ALP and TBA were reduced and the bile acid profiles in serum, liver and bile were improved significantly by OCA. This bile acid regulating effect of OCA was mainly based on increasing the expression of bile acid efflux transporters bile salt export pump (BSEP), multidrug resistant associated protein 2 (MRP2), MRP3 and multi-drug resistance 3 (MDR3) instead of bile acid synthesis inhibition. Furthermore, it was found that OCA reduced the activation and expression of Caspase 8/3 signaling pathway without the change of p-MLKL and BAX in LCA-induced cholestatic model. And the inhibition of Caspase 8/3 signaling pathway depended on the activation of Farnesoid X receptor (FXR) to inhibit Caspase 8 cleavage to form a active complex.Conclusions: This study found OCA improved LCA-induced cholestatic liver injury via FXR-induced exogenous cell apoptosis, which provided a new evidence for the application of OCA to ameliorate PBC in clinical.

scholarly journals Intestine farnesoid X receptor agonist and the gut microbiota activate G‐protein bile acid receptor‐1 signaling to improve metabolism

Hepatology ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 1574-1588 ◽  
Author(s):  
Preeti Pathak ◽  
Cen Xie ◽  
Robert G. Nichols ◽  
Jessica M. Ferrell ◽  
Shannon Boehme ◽  
...  
Keyword(s):  
Bile Acid ◽  
Gut Microbiota ◽  
G Protein ◽  
Receptor Agonist ◽  
Farnesoid X Receptor ◽  
Acid Receptor ◽  
Bile Acid Receptor

scholarly journals Obeticholic acid, a synthetic bile acid agonist of the farnesoid X receptor, attenuates experimental autoimmune encephalomyelitis

2016 ◽  
Vol 113 (6) ◽  
pp. 1600-1605 ◽  
Author(s):  
Peggy P. Ho ◽  
Lawrence Steinman
Keyword(s):  
T Cells ◽  
Bile Acid ◽  
Experimental Autoimmune Encephalomyelitis ◽  
B Cell ◽  
Chenodeoxycholic Acid ◽  
Farnesoid X Receptor ◽  
Cell Populations ◽  
Obeticholic Acid ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Bile acids are ligands for the nuclear hormone receptor, farnesoid X receptor (FXR). The bile acid–FXR interaction regulates bile acid synthesis, transport, and cholesterol metabolism. Recently, bile acid–FXR regulation has been reported to play an integral role in both hepatic and intestinal inflammation, and in atherosclerosis. In this study, we found that FXR knockout mice had more disease severity in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Obeticholic acid (6α-ethyl-chenodeoxycholic acid, 6-ECDCA), a synthetic FXR agonist, is an orally available drug that is currently in clinical trials for the treatment of inflammatory diseases such as alcoholic hepatitis, nonalcoholic steatohepatitis, and primary biliary cirrhosis. When we treated mice exhibiting established EAE with 6-ECDCA, or the natural FXR ligand chenodeoxycholic acid (CDCA), clinical disease was ameliorated by (i) suppressing lymphocyte activation and proinflammatory cytokine production; (ii) reducing CD4+ T cells and CD19+ B cell populations and their expression of negative checkpoint regulators programmed cell death protein 1 (PD1), programmed death-ligand 1 (PD-L1), and B and T lymphocyte attenuator (BTLA); (iii) increasing CD8+ T cells and PD1, PDl-1, and BTLA expression; and (iv) reducing VLA-4 expression in both the T- and B-cell populations. Moreover, adoptive transfer of 6-ECDCA– or CDCA-treated donor cells failed to transfer disease in naive recipients. Thus, we show that FXR functions as a negative regulator in neuroinflammation and we highlight that FXR agonists represent a potential previously unidentified therapy for MS.

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