The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity
Abstract
:1. Introduction
2. The Role of FXR in Bile Acid Homeostasis and Cholestasis
3. FXR, Fatty Acid Metabolism, and Lipotoxicity
3.1. Fatty Acid Synthesis and Metabolism
3.2. FXR and Non-Alcoholic Fatty Liver Disease (NAFLD)
3.3. FXR, Arachidonic Acid Breakdown, and Inflammation
4. FXR and Drug-Induced Hepatotoxicity
4.1. FXR and Drug-Induced Hepatocellular Injury
4.2. FXR in Drug-Induced Cholestasis
4.3. FXR and Drug ADME
5. FXR Agonists—A Double-Edged Sword
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ABCG | ATP binding cassette subfamily G |
ACC | Acetyl-CoA carboxylase |
AMPK | AMP-activated protein kinase |
APAP | Acetaminophen (Paracetamol) |
BA | Bile acid |
BSEP | Bile salt efflux pump |
CD36 | Cluster of differentiation 36; fatty acid translocase |
CoA | Coenzyme A |
CPT1 | Carnitine palmitoyltransferase-1 |
CYP | Cytochrome P450 superfamily |
DILI | Drug-induced liver injury |
EET | Epoxyeicosatrienoic acid |
EPHX2 | Epoxide hydrolase 2 |
FA | Fatty acid |
FABP | Fatty acid binding proteins |
FAS | Fatty acid synthetase |
FGF | Fibroblast growth factor |
FXR | Farnesoid X receptor |
HNF4α | Hepatocyte nuclear factor 4 alpha |
LDLr | Low-density lipoprotein receptor |
LRH-1 | Liver receptor homolog-1 |
LTB | Leukotriene |
MDR3 | Multidrug resistance protein 3 |
MRP | Multidrug resistance associated protein |
NAFLD | Nonalcoholic fatty liver disease |
NASH | Nonalcoholic steatohepatits |
NF-κB | Nuclear factor kappa B |
NTCP | Sodium-taurocholate cotransporting polypeptide |
OAT | Organic anion transporter |
OATP | Organic anion transporting polypeptides |
OCA | Obeticholic acid |
OCT | Organic cation transporter |
OSTα/β | Organic solute transporter alpha/beta |
PPAR | Peroxisome proliferator-activated receptor |
RXR | Retinoid X receptor |
SHP-1 | Small heterodimer protein 1 |
SIRT1 | Sirtuin 1; class III NAD+ dependent histone deacetylase |
SREBP-1c | Sterol regulatory element-binding protein 1c |
UGT | UDP-glucuronosyltransferase enzymes |
VLDL | Very-low density lipoprotein |
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Compound | Etiopathogenesis of Liver Disease | Type of Study | Outcome | Ref. |
---|---|---|---|---|
GW4064 | Acetaminophen-induced toxicity | Mouse |
| [126] |
GW4064 | Acetaminophen-induced toxicity | In vitro Mouse |
| [130] |
GW4064 | Amoxicillin/Clavulanic acid-induced toxicity | In vitro |
| [133] |
Schaftoside | Acetaminophen-induced toxicity | Mouse |
| [127] |
Saffron | Acetaminophen-induced toxicity | Rat |
| [128] |
OCA | Tripterygium-induced toxicity | Mouse |
| [131] |
OCA | Valproic acid-induced toxicity | In vitro Mouse |
| [132] |
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Rausch, M.; Samodelov, S.L.; Visentin, M.; Kullak-Ublick, G.A. The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity. Int. J. Mol. Sci. 2022, 23, 13967. https://doi.org/10.3390/ijms232213967
Rausch M, Samodelov SL, Visentin M, Kullak-Ublick GA. The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity. International Journal of Molecular Sciences. 2022; 23(22):13967. https://doi.org/10.3390/ijms232213967
Chicago/Turabian StyleRausch, Magdalena, Sophia L. Samodelov, Michele Visentin, and Gerd A. Kullak-Ublick. 2022. "The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity" International Journal of Molecular Sciences 23, no. 22: 13967. https://doi.org/10.3390/ijms232213967