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
APA StyleRausch, M., Samodelov, S. L., Visentin, M., & Kullak-Ublick, G. A. (2022). The Farnesoid X Receptor as a Master Regulator of Hepatotoxicity. International Journal of Molecular Sciences, 23(22), 13967. https://doi.org/10.3390/ijms232213967