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Bile acid nuclear receptor FXR and digestive system diseases
review-article
25 February 2015
Bile acids,
Farnesoid X receptor,
Gastrointestinal tract,
Inflammatory bowel disease,
Colorectal cancer,
Type 2 diabetes,
6-ECDCA, 6α-ethyl-chenodeoxycholic acid,
AF2, activation domain,
ANGTPL3, angiopoietin-like protein 3,
AOM, azoxymethane,
AP-1, activator protein-1,
Apo, apolipoprotein,
ASBT, apical sodium-dependent bile salt transporter,
BAAT, bile acid-CoA amino acid N-acetyltransferase,
BACS, bile acid-CoA synthetase,
BAs, bile acids,
BMI, body mass index,
BSEP, bile salt export pump,
CA, cholic acid,
CD, Crohn׳s disease,
CDCA, chenodeoxycholic acid,
CREB, cAMP regulatory element-binding protein,
CYP7A1, cholesterol 7α-hydroxylase,
db/db, diabetic mice,
DBD, DNA binding domain,
DCA, deoxycholic acid,
DSS, dextrane sodium sulfate,
ERK, extracellular signal-regulated kinase,
FABP6, fatty acid-binding protein subclass 6,
FFAs, free fatty acids,
FGF19, fibroblast growth factor 19,
FGFR4, fibroblast growth factor receptor 4,
FXR, farnesoid X receptor,
FXRE, farnesoid X receptor response element,
G6Pase, glucose-6-phosphatase,
GLP-1, glucagon-like peptide 1,
GLUT2, glucose transporter type 2,
GPBAR, G protein-coupled BA receptor,
GPCRs, G protein-coupled receptors,
GSK3, glycogen synthase kinase 3,
HDL-C, high density lipoprotein cholesterol,
HNF4α, hepatic nuclear factor 4α,
I-BABP, intestinal bile acid-binding protein,
IBD, inflammatory bowel disease,
IL-1, interleukin 1,
KLF11, Krüppel-like factor 11,
KRAS, Kirsten rat sarcoma viral oncogene homolog,
LBD, ligand binding domain,
LCA, lithocholic acid,
LRH-1, liver receptor homolog-1,
LPL, lipoprotein lipase,
MCA, muricholicacid,
MRP2, multidrug resistance-associated protein 2,
NF-κB, nuclear factor-kappa B,
NOD, non-obese diabetic,
NRs, nuclear receptors,
OSTα, organic solute transporter alpha,
OSTβ, organic solute transporter beta,
PEPCK, phosphoenol pyruvate carboxykinase,
PGC-1α, peroxisome proliferators-activated receptor γ coactivator protein-1α,
SHP, small heterodimer partner,
SREBP-1c, sterol regulatory element-binding protein 1c,
STAT3, signal transducers and activators of transcription 3,
T2D, type 2 diabetes,
TLCA, taurolithocholic acid,
TNBS, trinitrobenzensulfonic acid,
TNFα, tumor necrosis factors α,
UC, ulcerative colitis,
UDCA, ursodeoxycholic acid,
VSG, vertical sleeve gastrectomy
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Abstract
Bile acids (BAs) are not only digestive surfactants but also important cell signaling molecules, which stimulate several signaling pathways to regulate some important biological processes. The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), plays a pivotal role in regulating bile acid, lipid and glucose homeostasis as well as in regulating the inflammatory responses, barrier function and prevention of bacterial translocation in the intestinal tract. As expected, FXR is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, we discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases. Better understanding of the roles of FXR in digestive system will accelerate the development of FXR ligands/modulators for the treatment of digestive system diseases.
Graphical abstract
The bile-acid-activated nuclear receptor, farnesoid X receptor (FXR), is involved in the pathophysiology of a wide range of diseases of gastrointestinal tract, including inflammatory bowel disease, colorectal cancer and type 2 diabetes. In this review, authors discuss current knowledge of the roles of FXR in physiology of the digestive system and the related diseases.
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Most cited references106
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- Abstract: found
- Article: not found
Identification of a nuclear receptor for bile acids.
M. Makishima, A. Okamoto, J Repa … (1999)
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Bile acids: regulation of synthesis.
John Chiang (2009)
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Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis.
Author and article information
bile acids,farnesoid x receptor,gastrointestinal tract,inflammatory bowel disease,colorectal cancer,type 2 diabetes,6-ecdca, 6α-ethyl-chenodeoxycholic acid,af2, activation domain,angtpl3, angiopoietin-like protein 3,aom, azoxymethane,ap-1, activator protein-1,apo, apolipoprotein,asbt, apical sodium-dependent bile salt transporter,baat, bile acid-coa amino acid n-acetyltransferase,bacs, bile acid-coa synthetase,bas, bile acids,bmi, body mass index,bsep, bile salt export pump,ca, cholic acid,cd, crohn׳s disease,cdca, chenodeoxycholic acid,creb, camp regulatory element-binding protein,cyp7a1, cholesterol 7α-hydroxylase,db/db, diabetic mice,dbd, dna binding domain,dca, deoxycholic acid,dss, dextrane sodium sulfate,erk, extracellular signal-regulated kinase,fabp6, fatty acid-binding protein subclass 6,ffas, free fatty acids,fgf19, fibroblast growth factor 19,fgfr4, fibroblast growth factor receptor 4,fxr, farnesoid x receptor,fxre, farnesoid x receptor response element,g6pase, glucose-6-phosphatase,glp-1, glucagon-like peptide 1,glut2, glucose transporter type 2,gpbar, g protein-coupled ba receptor,gpcrs, g protein-coupled receptors,gsk3, glycogen synthase kinase 3,hdl-c, high density lipoprotein cholesterol,hnf4α, hepatic nuclear factor 4α,i-babp, intestinal bile acid-binding protein,ibd, inflammatory bowel disease,il-1, interleukin 1,klf11, krüppel-like factor 11,kras, kirsten rat sarcoma viral oncogene homolog,lbd, ligand binding domain,lca, lithocholic acid,lrh-1, liver receptor homolog-1,lpl, lipoprotein lipase,mca, muricholicacid,mrp2, multidrug resistance-associated protein 2,nf-κb, nuclear factor-kappa b,nod, non-obese diabetic,nrs, nuclear receptors,ostα, organic solute transporter alpha,ostβ, organic solute transporter beta,pepck, phosphoenol pyruvate carboxykinase,pgc-1α, peroxisome proliferators-activated receptor γ coactivator protein-1α,shp, small heterodimer partner,srebp-1c, sterol regulatory element-binding protein 1c,stat3, signal transducers and activators of transcription 3,t2d, type 2 diabetes,tlca, taurolithocholic acid,tnbs, trinitrobenzensulfonic acid,tnfα, tumor necrosis factors α,uc, ulcerative colitis,udca, ursodeoxycholic acid,vsg, vertical sleeve gastrectomy
bile acids, farnesoid x receptor, gastrointestinal tract, inflammatory bowel disease, colorectal cancer, type 2 diabetes, 6-ecdca, 6α-ethyl-chenodeoxycholic acid, af2, activation domain, angtpl3, angiopoietin-like protein 3, aom, azoxymethane, ap-1, activator protein-1, apo, apolipoprotein, asbt, apical sodium-dependent bile salt transporter, baat, bile acid-coa amino acid n-acetyltransferase, bacs, bile acid-coa synthetase, bas, bile acids, bmi, body mass index, bsep, bile salt export pump, ca, cholic acid, cd, crohn׳s disease, cdca, chenodeoxycholic acid, creb, camp regulatory element-binding protein, cyp7a1, cholesterol 7α-hydroxylase, db/db, diabetic mice, dbd, dna binding domain, dca, deoxycholic acid, dss, dextrane sodium sulfate, erk, extracellular signal-regulated kinase, fabp6, fatty acid-binding protein subclass 6, ffas, free fatty acids, fgf19, fibroblast growth factor 19, fgfr4, fibroblast growth factor receptor 4, fxr, farnesoid x receptor, fxre, farnesoid x receptor response element, g6pase, glucose-6-phosphatase, glp-1, glucagon-like peptide 1, glut2, glucose transporter type 2, gpbar, g protein-coupled ba receptor, gpcrs, g protein-coupled receptors, gsk3, glycogen synthase kinase 3, hdl-c, high density lipoprotein cholesterol, hnf4α, hepatic nuclear factor 4α, i-babp, intestinal bile acid-binding protein, ibd, inflammatory bowel disease, il-1, interleukin 1, klf11, krüppel-like factor 11, kras, kirsten rat sarcoma viral oncogene homolog, lbd, ligand binding domain, lca, lithocholic acid, lrh-1, liver receptor homolog-1, lpl, lipoprotein lipase, mca, muricholicacid, mrp2, multidrug resistance-associated protein 2, nf-κb, nuclear factor-kappa b, nod, non-obese diabetic, nrs, nuclear receptors, ostα, organic solute transporter alpha, ostβ, organic solute transporter beta, pepck, phosphoenol pyruvate carboxykinase, pgc-1α, peroxisome proliferators-activated receptor γ coactivator protein-1α, shp, small heterodimer partner, srebp-1c, sterol regulatory element-binding protein 1c, stat3, signal transducers and activators of transcription 3, t2d, type 2 diabetes, tlca, taurolithocholic acid, tnbs, trinitrobenzensulfonic acid, tnfα, tumor necrosis factors α, uc, ulcerative colitis, udca, ursodeoxycholic acid, vsg, vertical sleeve gastrectomy