Elsevier

Journal of Hepatology

Volume 58, Issue 1, January 2013, Pages 155-168
Journal of Hepatology

Review
Bile acid transporters and regulatory nuclear receptors in the liver and beyond

https://doi.org/10.1016/j.jhep.2012.08.002Get rights and content
Under a Creative Commons license
open access

Summary

Bile acid (BA) transporters are critical for maintenance of the enterohepatic BA circulation where BAs exert their multiple physiological functions including stimulation of bile flow, intestinal absorption of lipophilic nutrients, solubilization and excretion of cholesterol, as well as antimicrobial and metabolic effects. Tight regulation of BA transporters via nuclear receptors is necessary to maintain proper BA homeostasis. Hereditary and acquired defects of BA transporters are involved in the pathogenesis of several hepatobiliary disorders including cholestasis, gallstones, fatty liver disease and liver cancer, but also play a role in intestinal and metabolic disorders beyond the liver. Thus, pharmacological modification of BA transporters and their regulatory nuclear receptors opens novel treatment strategies for a wide range of disorders.

Keywords

Bile acids
Cholestasis
Fatty liver disease
Gallstones
Liver regeneration
Liver cancer

Abbreviations

6-ECDCA
6-ethylchenodeoxycholic acid
AE2
anion exchanger 2
ABCG5/8
cholesterol efflux pump, ATP-binding cassette, subfamily G, member 5/8
BA
bile acid
AMPK
AMP activated protein kinase
BCRP (ABCG2)
breast cancer resistance protein, ATP-binding cassette, subfamily G, member 2
BRIC
benign recurrent intrahepatic cholestasis
BSEP (ABCB11)
bile salt export pump
CAR (NR1I3)
constitutive androstane receptor
EGFR
epidermal growth factor receptor
FGF15/19
fibroblast growth factor 15/19
FXR (NR1H4)
farnesoid X receptor/bile acid receptor
GLP-1
glucagon like peptide 1
GR (NR3C1)
glucocorticoid receptor
HCC
hepatocellular carcinoma
HNF1α
hepatocyte nuclear factor 1 alpha
HNF4α (NR2A1)
hepatocyte nuclear factor 4 alpha
IBABP (FABP6, ILBP)
intestinal bile acid-binding protein, fatty acid-binding protein 6
ICP
intrahepatic cholestasis of pregnancy
IL6
interleukin 6
LCA
lithocholic acid
LRH-1 (NR5A2)
liver receptor homolog-1
LXRα (NR1H3)
liver X receptor alpha
MDR1 (ABCB1)
p-glycoprotein, ATP-binding cassette, subfamily B, member 1
Mdr2/MDR3 (ABCB4)
multidrug resistance protein 2 (rodents)/3 (human)
MRP2 (ABCC2)
multidrug resistance-associated protein 2, ATP-binding cassette, subfamily C, member 2
MRP3 (ABCC3)
multidrug resistance-associated protein 3, ATP-binding cassette, subfamily C, member 3
MRP4 (ABCC4)
multidrug resistance-associated protein 4, ATP-binding cassette, subfamily C, member 4
NAFLD
non-alcoholic fatty liver disease
NASH
non-alcoholic steatohepatitis
norUDCA
norursodeoxycholic acid
NR
nuclear receptor
NTCP (SLC10A1)
sodium/taurocholate cotransporting polypeptide, solute carrier family 10, member 1
OATP1A2 (SLCO1A2, OATP1, OATP-A, SLC21A3)
solute carrier organic anion transporter family, member 1A2
OATP1B1 (SLCO1B1, OATP2, OATP-C, SLC21A6)
solute carrier organic anion transporter family, member 1B1
OATP1B3 (SLCO1B3, OATP8, SLC21A8)
solute carrier organic anion transporter family, member 1B3
OSTαβ
organic solute transporter alpha/beta
PBC
primary biliary cirrhosis
PFIC
progressive familial intrahepatic cholestasis
PH
partial hepatectomy
PPARα (NR1C1)
peroxisome proliferator-activated receptor alpha
PPARγ (NR1C3)
peroxisome proliferator-activated receptor gamma
PSC
primary sclerosing cholangitis
PXR (NR1I2)
pregnane X receptor
RARα (NR1B1)
retinoic acid receptor alpha
RXRα (NR2B1)
retinoid X receptor alpha
SHP (NR0B2)
short heterodimer partner
SRC2
p160 steroid receptor coactivator
TGR5
G protein-coupled bile acid receptor
TNFα
tumor necrosis factor α
TPN
total parenteral nutrition
UDCA
ursodeoxycholic acid
VDR (NR1I1)
vitamin D receptor. Please note that for the convenience of better readability and clarity, abbreviations for transporters and nuclear receptors were capitalized throughout this article when symbols were identical for human and rodents

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