scholarly journals Farnesoid X receptor-induced lysine-specific histone demethylase reduces hepatic bile acid levels and protects the liver against bile acid toxicity

Hepatology ◽  
2015 ◽  
Vol 62 (1) ◽  
pp. 220-231 ◽  
Author(s):  
Young-Chae Kim ◽  
Sungsoon Fang ◽  
Sangwon Byun ◽  
Sunmi Seok ◽  
Byron Kemper ◽  
...  
Keyword(s):  
Bile Acid ◽  
Histone Demethylase ◽  
Farnesoid X Receptor ◽  
Hepatic Bile ◽  
Acid Toxicity

scholarly journals Recent advances in understanding bile acid homeostasis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2029 ◽  
Author(s):  
John YL Chiang
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Farnesoid X Receptor ◽  
Recent Advances ◽  
Bile Acid Pool Size ◽  
Bile Acid Receptor ◽  
Acid Toxicity ◽  
G Protein Coupled

Bile acids are derived from cholesterol to facilitate intestinal nutrient absorption and biliary secretion of cholesterol. Recent studies have identified bile acids as signaling molecules that activate nuclear farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (Gpbar-1, also known as TGR5) to maintain metabolic homeostasis and protect liver and other tissues and cells from bile acid toxicity. Bile acid homeostasis is regulated by a complex mechanism of feedback and feedforward regulation that is not completely understood. This review will cover recent advances in bile acid signaling and emerging concepts about the classic and alternative bile acid synthesis pathway, bile acid composition and bile acid pool size, and intestinal bile acid signaling and gut microbiome in regulation of bile acid homeostasis.

scholarly journals Complementary Roles of Farnesoid X Receptor, Pregnane X Receptor, and Constitutive Androstane Receptor in Protection against Bile Acid Toxicity

2003 ◽  
Vol 278 (46) ◽  
pp. 45062-45071 ◽  
Author(s):  
Grace L. Guo ◽  
Gilles Lambert ◽  
Masahiko Negishi ◽  
Jerrold M. Ward ◽  
H. Bryan Brewer ◽  
...  
Keyword(s):  
Bile Acid ◽  
Constitutive Androstane Receptor ◽  
Pregnane X Receptor ◽  
Farnesoid X Receptor ◽  
Acid Toxicity

scholarly journals Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine

2021 ◽  
Vol 7 (30) ◽  
pp. eabg1371
Author(s):  
Jia Wen ◽  
Gilberto Padilla Mercado ◽  
Alyssa Volland ◽  
Heidi L. Doden ◽  
Colin R. Lickwar ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Salts ◽  
Cell Types ◽  
Farnesoid X Receptor ◽  
Intestinal Lumen ◽  
Salt Composition ◽  
Hepatic Bile ◽  
Transport Pathways ◽  
Vertebrate Model

Bile salt synthesis, secretion into the intestinal lumen, and resorption in the ileum occur in all vertebrate classes. In mammals, bile salt composition is determined by host and microbial enzymes, affecting signaling through the bile salt–binding transcription factor farnesoid X receptor (Fxr). However, these processes in other vertebrate classes remain poorly understood. We show that key components of hepatic bile salt synthesis and ileal transport pathways are conserved and under control of Fxr in zebrafish. Zebrafish bile salts consist primarily of a C27 bile alcohol and a C24 bile acid that undergo multiple microbial modifications including bile acid deconjugation that augments Fxr activity. Using single-cell RNA sequencing, we provide a cellular atlas of the zebrafish intestinal epithelium and uncover roles for Fxr in transcriptional and differentiation programs in ileal and other cell types. These results establish zebrafish as a nonmammalian vertebrate model for studying bile salt metabolism and Fxr signaling.

Raised hepatic bile acid concentrations during pregnancy in mice are associated with reduced farnesoid X receptor function

Hepatology ◽  
2010 ◽  
Vol 52 (4) ◽  
pp. 1341-1349 ◽  
Author(s):  
Alexandra Milona ◽  
Bryn M. Owen ◽  
Jeremy F. L. Cobbold ◽  
Ellen C. L. Willemsen ◽  
Isobel J. Cox ◽  
...  
Keyword(s):  
Bile Acid ◽  
Farnesoid X Receptor ◽  
Receptor Function ◽  
Hepatic Bile

scholarly journals Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine

2020 ◽  
Author(s):  
Jia Wen ◽  
Gilberto Padilla Mercado ◽  
Alyssa Volland ◽  
Heidi L Doden ◽  
Colin R Lickwar ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Salt ◽  
Bile Salts ◽  
Cell Types ◽  
Farnesoid X Receptor ◽  
Intestinal Lumen ◽  
Salt Composition ◽  
Hepatic Bile ◽  
Transport Pathways ◽  
Vertebrate Model

Bile salt synthesis, secretion into the intestinal lumen, and resorption in the ileum occurs in all vertebrate classes. In mammals, bile salt composition is determined by host and microbial enzymes, affecting signaling through the bile salt-binding transcription factor Farnesoid X receptor (Fxr). However, these processes in other vertebrate classes remain poorly understood. We show that key components of hepatic bile salt synthesis and ileal transport pathways are conserved and under control of Fxr in zebrafish. Zebrafish bile salts consist primarily of a C27 bile alcohol and a C24 bile acid which undergo multiple microbial modifications including bile acid deconjugation that augments Fxr activity. Using single-cell RNA sequencing, we provide a cellular atlas of the zebrafish intestinal epithelium and uncover roles for Fxr in transcriptional and differentiation programs in ileal and other cell types. These results establish zebrafish as a non-mammalian vertebrate model for studying bile salt metabolism and Fxr signaling.

scholarly journals Hepatic Bile Acid Reuptake in the Rat Depends on Bile Acid Conjugation but Not on Agonistic Properties towards FXR and TGR5

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2371
Author(s):  
Samuel A. J. Trammell ◽  
Jens S. Svenningsen ◽  
Jens J. Holst ◽  
Matthew P. Gillum ◽  
Rune E. Kuhre
Keyword(s):  
Bile Acid ◽  
Portal Vein ◽  
Plasma Concentrations ◽  
Vena Cava ◽  
Farnesoid X Receptor ◽  
Hepatic Bile ◽  
Caval Vein ◽  
Inferior Caval Vein ◽  
G Protein Coupled ◽  
Vena Portae

Farnesoid X receptor (FXR) and Takeda G-protein coupled receptor 5 (TGR5) are the two known bile acid (BA) sensitive receptors and are expressed in the intestine and liver as well as in extra-enterohepatic tissues. The physiological effects of extra-enterohepatic FXR/TRG5 remain unclear. Further, the extent BAs escape liver reabsorption and how they interact with extra-enterohepatic FXR/TGR5 is understudied. We investigated if hepatic BA reuptake differed between BAs agonistic for FXR and TGR5 compared to non-agonists in the rat. Blood was collected from the portal vein and inferior caval vein from anesthetized rats before and 5, 20, 30, and 40 min post stimulation with sulfated cholecystokinin-8. Plasma concentrations of 20 different BAs were assessed by liquid chromatography coupled to mass spectrometry. Total portal vein BA AUC was 3–4 times greater than in the vena cava inferior (2.7 ± 0.6 vs. 0.7 ± 0.2 mM x min, p < 0.01, n = 8) with total unconjugated BAs being 2–3-fold higher than total conjugated BAs (AUC 8–10 higher p < 0.05 for both). However, in both cases, absolute ratios varied greatly among different BAs. The average hepatic reuptake of BAs agonistic for FXR/TGR5 was similar to non-agonists. However, as the sum of non-agonist BAs in vena portae was 2–3-fold higher than the sum agonist (p < 0.05), the peripheral BA pool was composed mostly of non-agonist BAs. We conclude that hepatic BA reuptake varies substantially by type and does not favor FXR/TGR5 BAs agonists.

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