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

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.

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 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 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.

scholarly journals Esterified and total 7 alpha-hydroxycholesterol in human serum as an indicator for hepatic bile acid synthesis.

1990 ◽  
Vol 31 (12) ◽  
pp. 2209-2218
Author(s):  
H Oda ◽  
H Yamashita ◽  
K Kosahara ◽  
S Kuroki ◽  
F Nakayama
Keyword(s):  
Bile Acid ◽  
Human Serum ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Hepatic Bile

scholarly journals Role of Bile Acids in the Regulation of Food Intake, and Their Dysregulation in Metabolic Disease

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1104
Author(s):  
Cong Xie ◽  
Weikun Huang ◽  
Richard L. Young ◽  
Karen L. Jones ◽  
Michael Horowitz ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Peptide Yy ◽  
Glycogen Synthesis ◽  
Hormone Secretion ◽  
Gastrointestinal Hormones ◽  
Farnesoid X Receptor ◽  
Gastrointestinal Hormone ◽  
Bile Acid Sequestrants

Bile acids are cholesterol-derived metabolites with a well-established role in the digestion and absorption of dietary fat. More recently, the discovery of bile acids as natural ligands for the nuclear farnesoid X receptor (FXR) and membrane Takeda G-protein-coupled receptor 5 (TGR5), and the recognition of the effects of FXR and TGR5 signaling have led to a paradigm shift in knowledge regarding bile acid physiology and metabolic health. Bile acids are now recognized as signaling molecules that orchestrate blood glucose, lipid and energy metabolism. Changes in FXR and/or TGR5 signaling modulates the secretion of gastrointestinal hormones including glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), hepatic gluconeogenesis, glycogen synthesis, energy expenditure, and the composition of the gut microbiome. These effects may contribute to the metabolic benefits of bile acid sequestrants, metformin, and bariatric surgery. This review focuses on the role of bile acids in energy intake and body weight, particularly their effects on gastrointestinal hormone secretion, the changes in obesity and T2D, and their potential relevance to the management of metabolic disorders.

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