Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review)
- Authors:
- Yanning Sun
- Kai Sun
- Hongju Ling
- Qinghua Xia
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Affiliations: Urology Department, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China - Published online on: May 12, 2025 https://doi.org/10.3892/ijmm.2025.5551
- Article Number: 110
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Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
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Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schütz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P and Evans RM: The nuclear receptor superfamily: The second decade. Cell. 83:835–839. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, Burka LT, McMorris T, Lamph WW, et al: Identification of a nuclear receptor that is activated by farnesol metabolites. Cell. 81:687–693. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Parks DJ, Blanchard SG, Bledsoe RK, Chandra G, Consler TG, Kliewer SA, Stimmel JB, Willson TM, Zavacki AM, Moore DD and Lehmann JM: Bile acids: Natural ligands for an orphan nuclear receptor. Science. 284:1365–1368. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Wang H, Chen J, Hollister K, Sowers LC and Forman BM: Endogenous bile acids are ligands for the nuclear receptor FXR/BAR. Mol Cell. 3:543–553. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Chávez-Talavera O, Tailleux A, Lefebvre P and Staels B: Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease. Gastroenterology. 152:1679–1694.e3. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Mencarelli A and Fiorucci S: FXR an emerging therapeutic target for the treatment of atherosclerosis. J Cell Mol Med. 14:79–92. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Wu Q, Sun L, Hu X, Wang X, Xu F, Chen B, Liang X, Xia J, Wang P, Aibara D, et al: Suppressing the intestinal farnesoid X receptor/sphingomyelin phosphodiesterase 3 axis decreases atherosclerosis. J Clin Invest. 131:e1428652021. View Article : Google Scholar : PubMed/NCBI | |
|
Glass CK: Differential recognition of target genes by nuclear receptor monomers, dimers, and heterodimers. Endocr Rev. 15:391–407. 1994.PubMed/NCBI | |
|
Downes M, Verdecia MA, Roecker AJ, Hughes R, Hogenesch JB, Kast-Woelbern HR, Bowman ME, Ferrer JL, Anisfeld AM, Edwards PA, et al: A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol Cell. 11:1079–1092. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Mi LZ, Devarakonda S, Harp JM, Han Q, Pellicciari R, Willson TM, Khorasanizadeh S and Rastinejad F: Structural basis for bile acid binding and activation of the nuclear receptor FXR. Mol Cell. 11:1093–1100. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang L, Zhang H, Xiao D, Wei H and Chen Y: Farnesoid X receptor (FXR): Structures and ligands. Comput Struct Biotechnol J. 19:2148–2159. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Tian SY, Chen SM, Pan CX and Li Y: FXR: Structures, biology, and drug development for NASH and fibrosis diseases. Acta Pharmacol Sin. 43:1120–1132. 2022. View Article : Google Scholar : PubMed/NCBI | |
|
Otte K, Kranz H, Kober I, Thompson P, Hoefer M, Haubold B, Remmel B, Voss H, Kaiser C, Albers M, et al: Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol. Mol Cell Biol. 23:864–872. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Huber RM, Murphy K, Miao B, Link JR, Cunningham MR, Rupar MJ, Gunyuzlu PL, Haws TF, Kassam A, Powell F, et al: Generation of multiple farnesoid-X-receptor isoforms through the use of alternative promoters. Gene. 290:35–43. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y, Kast-Woelbern HR and Edwards PA: Natural structural variants of the nuclear receptor farnesoid X receptor affect transcriptional activation. J Biol Chem. 278:104–110. 2003. View Article : Google Scholar | |
|
Vaquero J, Monte MJ, Dominguez M, Muntané J and Marin JJ: Differential activation of the human farnesoid X receptor depends on the pattern of expressed isoforms and the bile acid pool composition. Biochem Pharmacol. 86:926–939. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Chen Y, Song X, Valanejad L, Vasilenko A, More V, Qiu X, Chen W, Lai Y, Slitt A, Stoner M, et al: Bile salt export pump is dysregulated with altered farnesoid X receptor isoform expression in patients with hepatocellular carcinoma. Hepatology. 57:1530–1541. 2013. View Article : Google Scholar | |
|
Correia JC, Massart J, de Boer JF, Porsmyr-Palmertz M, Martínez-Redondo V, Agudelo LZ, Sinha I, Meierhofer D, Ribeiro V, Björnholm M, et al: Bioenergetic cues shift FXR splicing towards FXRα2 to modulate hepatic lipolysis and fatty acid metabolism. Mol Metab. 4:891–902. 2015. View Article : Google Scholar | |
|
Massafra V and van Mil SWC: Farnesoid X receptor: A 'homeostat' for hepatic nutrient metabolism. Biochim Biophys Acta Mol Basis Dis. 1864:45–59. 2018. View Article : Google Scholar | |
|
Marzolini C, Tirona RG, Gervasini G, Poonkuzhali B, Assem M, Lee W, Leake BF, Schuetz JD, Schuetz EG and Kim RB: A common polymorphism in the bile acid receptor farnesoid X receptor is associated with decreased hepatic target gene expression. Mol Endocrinol. 21:1769–1780. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Ruscica M, Busnelli M, Runfola E, Corsini A and Sirtori CR: Impact of PPAR-Alpha polymorphisms-the case of metabolic disorders and atherosclerosis. Int J Mol Sci. 20:43782019. View Article : Google Scholar : PubMed/NCBI | |
|
Meirhaeghe A and Amouyel P: Impact of genetic variation of PPARgamma in humans. Mol Genet Metab. 83:93–102. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Valdivielso JM and Fernandez E: Vitamin D receptor polymorphisms and diseases. Clin Chim Acta. 371:1–12. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Dahlman I, Nilsson M, Jiao H, Hoffstedt J, Lindgren CM, Humphreys K, Kere J, Gustafsson JA, Arner P and Dahlman-Wright K: Liver X receptor gene polymorphisms and adipose tissue expression levels in obesity. Pharmacogenet Genomics. 16:881–889. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Nishigori H, Tomura H, Tonooka N, Kanamori M, Yamada S, Sho K, Inoue I, Kikuchi N, Onigata K, Kojima I, et al: Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects. Proc Natl Acad Sci USA. 98:575–580. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Vaxillaire M, Rouard M, Yamagata K, Oda N, Kaisaki PJ, Boriraj VV, Chevre JC, Boccio V, Cox RD, Lathrop GM, et al: Identification of nine novel mutations in the hepatocyte nuclear factor 1 alpha gene associated with maturity-onset diabetes of the young (MODY3). Hum Mol Genet. 6:583–586. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Yamagata K, Furuta H, Oda N, Kaisaki PJ, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M and Bell GI: Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature. 384:458–460. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
van Mil SW, Milona A, Dixon PH, Mullenbach R, Geenes VL, Chambers J, Shevchuk V, Moore GE, Lammert F, Glantz AG, et al: Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy. Gastroenterology. 133:507–516. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Edwards PA, Kast HR and Anisfeld AM: BAREing it all: The adoption of LXR and FXR and their roles in lipid homeostasis. J Lipid Res. 43:2–12. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Laffitte BA, Kast HR, Nguyen CM, Zavacki AM, Moore DD and Edwards PA: Identification of the DNA binding specificity and potential target genes for the farnesoid X-activated receptor. J Biol Chem. 275:10638–10647. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Chen WD, Wang YD, Zhang L, Shiah S, Wang M, Yang F, Yu D, Forman BM and Huang W: Farnesoid X receptor alleviates age-related proliferation defects in regenerating mouse livers by activating forkhead box m1b transcription. Hepatology. 51:953–962. 2010. View Article : Google Scholar | |
|
Gautier T, de Haan W, Grober J, Ye D, Bahr MJ, Claudel T, Nijstad N, Van Berkel TJC, Havekes LM, Manns MP, et al: Farnesoid X receptor activation increases cholesteryl ester transfer protein expression in humans and transgenic mice. J Lipid Res. 54:2195–2205. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Anisfeld AM, Kast-Woelbern HR, Meyer ME, Jones SA, Zhang Y, Williams KJ, Willson T and Edwards PA: Syndecan-1 expression is regulated in an isoform-specific manner by the farnesoid-X receptor. J Biol Chem. 278:20420–20428. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Thomas AM, Hart SN, Kong B, Fang J, Zhong XB and Guo GL: Genome-wide tissue-specific farnesoid X receptor binding in mouse liver and intestine. Hepatology. 51:1410–1419. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Panzitt K and Wagner M: FXR in liver physiology: Multiple faces to regulate liver metabolism. Biochim Biophys Acta Mol Basis Dis. 1867:1661332021. View Article : Google Scholar : PubMed/NCBI | |
|
Anisfeld AM, Kast-Woelbern HR, Lee H, Zhang Y, Lee FY and Edwards PA: Activation of the nuclear receptor FXR induces fibrinogen expression: A new role for bile acid signaling. J Lipid Res. 46:458–468. 2005. View Article : Google Scholar | |
|
Zhao A, Lew JL, Huang L, Yu J, Zhang T, Hrywna Y, Thompson JR, de Pedro N, Blevins RA, Peláez F, et al: Human kininogen gene is transactivated by the farnesoid X receptor. J Biol Chem. 278:28765–28770. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang X, Huang S, Gao M, Liu J, Jia X, Han Q, Zheng S, Miao Y, Li S, Weng H, et al: Farnesoid X receptor (FXR) gene deficiency impairs urine concentration in mice. Proc Natl Acad Sci USA. 111:2277–2282. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Jiang T, Wang XX, Scherzer P, Wilson P, Tallman J, Takahashi H, Li J, Iwahashi M, Sutherland E, Arend L and Levi M: Farnesoid X receptor modulates renal lipid metabolism, fibrosis, and diabetic nephropathy. Diabetes. 56:2485–2493. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Glatz JFC and Luiken J: Dynamic role of the transmembrane glycoprotein CD36 (SR-B2) in cellular fatty acid uptake and utilization. J Lipid Res. 59:1084–1093. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Wilson CG, Tran JL, Erion DM, Vera NB, Febbraio M and Weiss EJ: Hepatocyte-specific disruption of CD36 attenuates fatty liver and improves insulin sensitivity in HFD-fed mice. Endocrinology. 157:570–585. 2016. View Article : Google Scholar : | |
|
Zhou J, Febbraio M, Wada T, Zhai Y, Kuruba R, He J, Lee JH, Khadem S, Ren S, Li S, et al: Hepatic fatty acid transporter Cd36 is a common target of LXR, PXR, and PPARgamma in promoting steatosis. Gastroenterology. 134:556–567. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Ma Y, Huang Y, Yan L, Gao M and Liu D: Synthetic FXR agonist GW4064 prevents diet-induced hepatic steatosis and insulin resistance. Pharm Res. 30:1447–1457. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Chen S, Sun S, Feng Y, Li X, Yin G, Liang P, Yu W, Meng D, Zhang X, Liu H and Zhang F: Diosgenin attenuates nonalcoholic hepatic steatosis through the hepatic FXR-SHP-SREBP1C/PPARα/CD36 pathway. Eur J Pharmacol. 952:1758082023. View Article : Google Scholar | |
|
Mastrodonato M, Calamita G, Rossi R, Mentino D, Bonfrate L, Portincasa P, Ferri D and Liquori GE: Altered distribution of caveolin-1 in early liver steatosis. Eur J Clin Invest. 41:642–651. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Fernández-Rojo MA, Restall C, Ferguson C, Martel N, Martin S, Bosch M, Kassan A, Leong GM, Martin SD, McGee SL, et al: Caveolin-1 orchestrates the balance between glucose and lipid-dependent energy metabolism: Implications for liver regeneration. Hepatology. 55:1574–1584. 2012. View Article : Google Scholar | |
|
Fernández-Rojo MA, Gongora M, Fitzsimmons RL, Martel N, Martin SD, Nixon SJ, Brooks AJ, Ikonomopoulou MP, Martin S, Lo HP, et al: Caveolin-1 is necessary for hepatic oxidative lipid metabolism: Evidence for crosstalk between caveolin-1 and bile acid signaling. Cell Rep. 4:238–247. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Motojima K, Passilly P, Peters JM, Gonzalez FJ and Latruffe N: Expression of putative fatty acid transporter genes are regulated by peroxisome proliferator-activated receptor alpha and gamma activators in a tissue- and inducer-specific manner. J Biol Chem. 273:16710–16744. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Acharya R, Shetty SS and Kumari NS: Fatty acid transport proteins (FATPs) in cancer. Chem Phys Lipids. 250:1052692023. View Article : Google Scholar | |
|
Hirsch D, Stahl A and Lodish HF: A family of fatty acid transporters conserved from mycobacterium to man. Proc Natl Acad Sci USA. 95:8625–8629. 1998. View Article : Google Scholar : PubMed/NCBI | |
|
Falcon A, Doege H, Fluitt A, Tsang B, Watson N, Kay MA and Stahl A: FATP2 is a hepatic fatty acid transporter and peroxisomal very long-chain acyl-CoA synthetase. Am J Physiol Endocrinol Metab. 299:E384–E393. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Lee Y, Kim BR, Kang GH, Lee GJ, Park YJ, Kim H, Jang HC and Choi SH: The effects of PPAR agonists on atherosclerosis and nonalcoholic fatty liver disease in ApoE-/-FXR-/- mice. Endocrinol Metab (Seoul). 36:1243–1253. 2021. View Article : Google Scholar | |
|
Savage DB, Choi CS, Samuel VT, Liu ZX, Zhang D, Wang A, Zhang XM, Cline GW, Yu XX, Geisler JG, et al: Reversal of diet-induced hepatic steatosis and hepatic insulin resistance by antisense oligonucleotide inhibitors of acetyl-CoA carboxylases 1 and 2. J Clin Invest. 116:817–824. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Dentin R, Benhamed F, Hainault I, Fauveau V, Foufelle F, Dyck JR, Girard J and Postic C: Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice. Diabetes. 55:2159–2170. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Yahagi N, Shimano H, Hasty AH, Matsuzaka T, Ide T, Yoshikawa T, Amemiya-Kudo M, Tomita S, Okazaki H, Tamura Y, et al: Absence of sterol regulatory element-binding protein-1 (SREBP-1) ameliorates fatty livers but not obesity or insulin resistance in Lep(ob)/Lep(ob) mice. J Biol Chem. 277:19353–19357. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Ma K, Saha PK, Chan L and Moore DD: Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest. 116:1102–1109. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Watanabe M, Houten SM, Wang L, Moschetta A, Mangelsdorf DJ, Heyman RA, Moore DD and Auwerx J: Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c. J Clin Invest. 113:1408–1418. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Iizuka K, Takao K and Yabe D: ChREBP-mediated regulation of lipid metabolism: Involvement of the gut microbiota, liver, and adipose tissue. Front Endocrinol (Lausanne). 11:5871892020. View Article : Google Scholar : PubMed/NCBI | |
|
Caron S, Huaman Samanez C, Dehondt H, Ploton M, Briand O, Lien F, Dorchies E, Dumont J, Postic C, Cariou B, et al: Farnesoid X receptor inhibits the transcriptional activity of carbohydrate response element binding protein in human hepatocytes. Mol Cell Biol. 33:2202–2211. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Kliewer SA and Mangelsdorf DJ: Bile acids as hormones: The FXR-FGF15/19 pathway. Dig Dis. 33:327–331. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Beenken A and Mohammadi M: The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 8:235–253. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Montagner A, Polizzi A, Fouché E, Ducheix S, Lippi Y, Lasserre F, Barquissau V, Régnier M, Lukowicz C, Benhamed F, et al: Liver PPARα is crucial for whole-body fatty acid homeostasis and is protective against NAFLD. Gut. 65:1202–1214. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Prawitt J, Abdelkarim M, Stroeve JH, Popescu I, Duez H, Velagapudi VR, Dumont J, Bouchaert E, van Dijk TH, Lucas A, et al: Farnesoid X receptor deficiency improves glucose homeostasis in mouse models of obesity. Diabetes. 60:1861–1871. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Pineda Torra I, Claudel T, Duval C, Kosykh V, Fruchart JC and Staels B: Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor. Mol Endocrinol. 17:259–272. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Xu J, Li Y, Chen WD, Xu Y, Yin L, Ge X, Jadhav K, Adorini L and Zhang Y: Hepatic carboxylesterase 1 is essential for both normal and farnesoid X receptor-controlled lipid homeostasis. Hepatology. 59:1761–1771. 2014. View Article : Google Scholar | |
|
Liu Y, Song A, Yang X, Zhen Y, Chen W, Yang L, Wang C and Ma H: Farnesoid X receptor agonist decreases lipid accumulation by promoting hepatic fatty acid oxidation in db/db mice. Int J Mol Med. 42:1723–1731. 2018.PubMed/NCBI | |
|
Fernandez-Marcos PJ and Auwerx J: Regulation of PGC-1alpha, a nodal regulator of mitochondrial biogenesis. Am J Clin Nutr. 93:884s–890s. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang C, Deng J, Liu D, Tuo X, Xiao L, Lai B, Yao Q, Liu J, Yang H and Wang N: Nuciferine ameliorates hepatic steatosis in high-fat diet/streptozocin-induced diabetic mice through a PPARα/PPARγ coactivator-1α pathway. Br J Pharmacol. 175:4218–4228. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang Y, Castellani LW, Sinal CJ, Gonzalez FJ and Edwards PA: Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha) regulates triglyceride metabolism by activation of the nuclear receptor FXR. Genes Dev. 18:157–169. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Rizzolo D, Kong B, Taylor RE, Brinker A, Goedken M, Buckley B and Guo GL: Bile acid homeostasis in female mice deficient in Cyp7a1 and Cyp27a1. Acta Pharm Sin B. 11:3847–3856. 2021. View Article : Google Scholar | |
|
Goodwin B, Jones SA, Price RR, Watson MA, McKee DD, Moore LB, Galardi C, Wilson JG, Lewis MC, Roth ME, et al: A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis. Mol Cell. 6:517–526. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Chiang JY: Bile acid regulation of gene expression: Roles of nuclear hormone receptors. Endocr Rev. 23:443–463. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Kong B, Wang L, Chiang JY, Zhang Y, Klaassen CD and Guo GL: Mechanism of tissue-specific farnesoid X receptor in suppressing the expression of genes in bile-acid synthesis in mice. Hepatology. 56:1034–1043. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Lee FY, Lee H, Hubbert ML, Edwards PA and Zhang Y: FXR, a multipurpose nuclear receptor. Trends Biochem Sci. 31:572–580. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Cai SY and Boyer JL: FXR: A target for cholestatic syndromes? Expert Opin Ther Targets. 10:409–421. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Kast HR, Goodwin B, Tarr PT, Jones SA, Anisfeld AM, Stoltz CM, Tontonoz P, Kliewer S, Willson TM and Edwards PA: Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor farnesoid X-activated receptor and constitutive androstane receptor. J Biol Chem. 277:2908–2915. 2002. View Article : Google Scholar | |
|
Huang L, Zhao A, Lew JL, Zhang T, Hrywna Y, Thompson JR, de Pedro N, Royo I, Blevins RA, Peláez F, et al: Farnesoid X receptor activates transcription of the phospholipid pump MDR3. J Biol Chem. 278:51085–51090. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Sinal CJ, Tohkin M, Miyata M, Ward JM, Lambert G and Gonzalez FJ: Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis. Cell. 102:731–744. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Denke MA and Grundy SM: Hypertriglyceridemia: A relative contraindication to the use of bile acid-binding resins? Hepatology. 8:974–975. 1988. View Article : Google Scholar : PubMed/NCBI | |
|
Hirokane H, Nakahara M, Tachibana S, Shimizu M and Sato R: Bile acid reduces the secretion of very low density lipoprotein by repressing microsomal triglyceride transfer protein gene expression mediated by hepatocyte nuclear factor-4. J Biol Chem. 279:45685–45692. 2004. View Article : Google Scholar : PubMed/NCBI | |
|
Liu Q, Yang M, Fu X, Liu R, Sun C, Pan H, Wong CW and Guan M: Activation of farnesoid X receptor promotes triglycerides lowering by suppressing phospholipase A2 G12B expression. Mol Cell Endocrinol. 436:93–101. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Giammanco A, Spina R, Cefalù AB and Averna M: APOC-III: A gatekeeper in controlling triglyceride metabolism. Curr Atheroscler Rep. 25:67–76. 2023. View Article : Google Scholar : PubMed/NCBI | |
|
Claudel T, Inoue Y, Barbier O, Duran-Sandoval D, Kosykh V, Fruchart J, Fruchart JC, Gonzalez FJ and Staels B: Farnesoid X receptor agonists suppress hepatic apolipoprotein CIII expression. Gastroenterology. 125:544–555. 2003. View Article : Google Scholar : PubMed/NCBI | |
|
Kast HR, Nguyen CM, Sinal CJ, Jones SA, Laffitte BA, Reue K, Gonzalez FJ, Willson TM and Edwards PA: Farnesoid X-activated receptor induces apolipoprotein C-II transcription: A molecular mechanism linking plasma triglyceride levels to bile acids. Mol Endocrinol. 15:1720–1728. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Mak PA, Kast-Woelbern HR, Anisfeld AM and Edwards PA: Identification of PLTP as an LXR target gene and apoE as an FXR target gene reveals overlapping targets for the two nuclear receptors. J Lipid Res. 43:2037–2041. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Urizar NL, Dowhan DH and Moore DD: The farnesoid X-activated receptor mediates bile acid activation of phospholipid transfer protein gene expression. J Biol Chem. 275:39313–39317. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Kim I, Morimura K, Shah Y, Yang Q, Ward JM and Gonzalez FJ: Spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice. Carcinogenesis. 28:940–946. 2007. View Article : Google Scholar | |
|
Yang F, Huang X, Yi T, Yen Y, Moore DD and Huang W: Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor. Cancer Res. 67:863–867. 2007. View Article : Google Scholar : PubMed/NCBI | |
|
Su H, Ma C, Liu J, Li N, Gao M, Huang A, Wang X, Huang W and Huang X: Downregulation of nuclear receptor FXR is associated with multiple malignant clinicopathological characteristics in human hepatocellular carcinoma. Am J Physiol Gastrointest Liver Physiol. 303:G1245–G1253. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Takahashi S, Tanaka N, Fukami T, Xie C, Yagai T, Kim D, Velenosi TJ, Yan T, Krausz KW, Levi M and Gonzalez FJ: Role of Farnesoid X Receptor and Bile Acids in Hepatic Tumor Development. Hepatol Commun. 2:1567–1582. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Kong B, Zhu Y, Li G, Williams JA, Buckley K, Tawfik O, Luyendyk JP and Guo GL: Mice with hepatocyte-specific FXR deficiency are resistant to spontaneous but susceptible to cholic acid-induced hepatocarcinogenesis. Am J Physiol Gastrointest Liver Physiol. 310:G295–G302. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Degirolamo C, Modica S, Vacca M, Di Tullio G, Morgano A, D'Orazio A, Kannisto K, Parini P and Moschetta A: Prevention of spontaneous hepatocarcinogenesis in farnesoid X receptor-null mice by intestinal-specific farnesoid X receptor reactivation. Hepatology. 61:161–170. 2015. View Article : Google Scholar | |
|
Li G, Kong B, Zhu Y, Zhan L, Williams JA, Tawfik O, Kassel KM, Luyendyk JP, Wang L and Guo GL: Small heterodimer partner overexpression partially protects against liver tumor development in farnesoid X receptor knockout mice. Toxicol Appl Pharmacol. 272:299–305. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Režen T, Rozman D, Kovács T, Kovács P, Sipos A, Bai P and Mikó E: The role of bile acids in carcinogenesis. Cell Mol Life Sci. 79:2432022. View Article : Google Scholar | |
|
Ooi GJ, Meikle PJ, Huynh K, Earnest A, Roberts SK, Kemp W, Parker BL, Brown W, Burton P and Watt MJ: Hepatic lipidomic remodeling in severe obesity manifests with steatosis and does not evolve with non-alcoholic steatohepatitis. J Hepatol. 75:524–535. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Nobili V, Alisi A, Mosca A, Della Corte C, Veraldi S, De Vito R, De Stefanis C, D'Oria V, Jahnel J, Zohrer E, et al: Hepatic farnesoid X receptor protein level and circulating fibroblast growth factor 19 concentration in children with NAFLD. Liver Int. 38:342–349. 2018. View Article : Google Scholar | |
|
Aguilar-Olivos NE, Carrillo-Córdova D, Oria-Hernández J, Sánchez-Valle V, Ponciano-Rodríguez G, Ramírez-Jaramillo M, Chablé-Montero F, Chávez-Tapia NC, Uribe M and Méndez-Sánchez N: The nuclear receptor FXR, but not LXR, up-regulates bile acid transporter expression in non-alcoholic fatty liver disease. Ann Hepatol. 14:487–493. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Neuschwander-Tetri BA, Loomba R, Sanyal AJ, Lavine JE, Van Natta ML, Abdelmalek MF, Chalasani N, Dasarathy S, Diehl AM and Hameed B, et al: Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): A multicentre, randomised, placebo-controlled trial. Lancet. 385:956–965. 2015. View Article : Google Scholar : | |
|
Tully DC, Rucker PV, Chianelli D, Williams J, Vidal A, Alper PB, Mutnick D, Bursulaya B, Schmeits J, Wu X, et al: Discovery of tropifexor (LJN452), a highly potent non-bile acid FXR agonist for the treatment of cholestatic liver diseases and nonalcoholic steatohepatitis (NASH). J Med Chem. 60:9960–9973. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Zhang S, Wang J, Liu Q and Harnish DC: Farnesoid X receptor agonist WAY-362450 attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis. J Hepatol. 51:380–388. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Wang J, Yang N and Xu Y: Natural products in the modulation of farnesoid X receptor against nonalcoholic fatty liver disease. Am J Chin Med. 52:291–314. 2024. View Article : Google Scholar : PubMed/NCBI | |
|
Huang W, Cao Z, Wang W, Yang Z, Jiao S, Chen Y, Chen S, Zhang L and Li Z: Discovery of LH10, a novel fexaramine-based FXR agonist for the treatment of liver disease. Bioorg Chem. 143:1070712024. View Article : Google Scholar : PubMed/NCBI | |
|
Qin X, Tan Y, Ren W, Zhou W, Niu R, Liang L, Li J, Cao K, Wei G, Zhu X and Huang M: Elevated expression of LCN13 through FXR activation ameliorates hepatocellular lipid accumulation and inflammation. Int Immunopharmacol. 131:1118122024. View Article : Google Scholar : PubMed/NCBI | |
|
Huang XF, Zhao WY and Huang WD: FXR and liver carcinogenesis. Acta Pharmacol Sin. 36:37–43. 2015. View Article : Google Scholar : | |
|
Sayin SI, Wahlström A, Felin J, Jäntti S, Marschall HU, Bamberg K, Angelin B, Hyötyläinen T, Orešič M and Bäckhed F: Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 17:225–235. 2013. View Article : Google Scholar : PubMed/NCBI | |
|
Ma Y, Zhang Y, Qu R, Zhou X, Sun L, Wang K, Jiang C, Zhang Z and Fu W: Promotion of Deoxycholic acid effect on colonic cancer cell lines in vitro by altering the mucosal microbiota. Microorganisms. 10:24862022. View Article : Google Scholar : PubMed/NCBI | |
|
Bailey AM, Zhan L, Maru D, Shureiqi I, Pickering CR, Kiriakova G, Izzo J, He N, Wei C, Baladandayuthapani V, et al: FXR silencing in human colon cancer by DNA methylation and KRAS signaling. Am J Physiol Gastrointest Liver Physiol. 306:G48–G58. 2014. View Article : Google Scholar : | |
|
Guo S, Peng Y, Lou Y, Cao L, Liu J, Lin N, Cai S, Kang Y, Zeng S and Yu L: Downregulation of the farnesoid X receptor promotes colorectal tumorigenesis by facilitating enterotoxigenic Bacteroides fragilis colonization. Pharmacol Res. 177:1061012022. View Article : Google Scholar : PubMed/NCBI | |
|
Chung L, Thiele Orberg E, Geis AL, Chan JL, Fu K, DeStefano Shields CE, Dejea CM, Fathi P, Chen J, Finard BB, et al: Bacteroides fragilis toxin coordinates a pro-carcinogenic inflammatory cascade via targeting of colonic epithelial cells. Cell Host Microbe. 23:203–214.e5. 2018. View Article : Google Scholar : PubMed/NCBI | |
|
Wu S, Rhee KJ, Albesiano E, Rabizadeh S, Wu X, Yen HR, Huso DL, Brancati FL, Wick E, McAllister F, et al: A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses. Nat Med. 15:1016–1022. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Dong X, Qi M, Cai C, Zhu Y, Li Y, Coulter S, Sun F, Liddle C, Uboha NV, Halberg R, et al: Farnesoid X receptor mediates macrophage-intrinsic responses to suppress colitis-induced colon cancer progression. JCI Insight. 9:e1704282024. View Article : Google Scholar : PubMed/NCBI | |
|
Gadaleta RM, van Erpecum KJ, Oldenburg B, Willemsen EC, Renooij W, Murzilli S, Klomp LW, Siersema PD, Schipper ME, Danese S, et al: Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease. Gut. 60:463–472. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Absil L, Journé F, Larsimont D, Body JJ, Tafforeau L and Nonclercq D: Farnesoid X receptor as marker of osteotropism of breast cancers through its role in the osteomimetism of tumor cells. BMC Cancer. 20:6402020. View Article : Google Scholar : PubMed/NCBI | |
|
Silva J, Dasgupta S, Wang G, Krishnamurthy K, Ritter E and Bieberich E: Lipids isolated from bone induce the migration of human breast cancer cells. J Lipid Res. 47:724–733. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Krishnamurthy K, Wang G, Rokhfeld D and Bieberich E: Deoxycholate promotes survival of breast cancer cells by reducing the level of pro-apoptotic ceramide. Breast Cancer Res. 10:R1062008. View Article : Google Scholar : PubMed/NCBI | |
|
Swales KE, Korbonits M, Carpenter R, Walsh DT, Warner TD and Bishop-Bailey D: The farnesoid X receptor is expressed in breast cancer and regulates apoptosis and aromatase expression. Cancer Res. 66:10120–10126. 2006. View Article : Google Scholar : PubMed/NCBI | |
|
Alasmael N, Mohan R, Meira LB, Swales KE and Plant NJ: Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential. Cancer Lett. 370:250–259. 2016. View Article : Google Scholar | |
|
Giordano C, Catalano S, Panza S, Vizza D, Barone I, Bonofiglio D, Gelsomino L, Rizza P, Fuqua SA and Andò S: Farnesoid X receptor inhibits tamoxifen-resistant MCF-7 breast cancer cell growth through downregulation of HER2 expression. Oncogene. 30:4129–4140. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Giordano C, Barone I, Vircillo V, Panza S, Malivindi R, Gelsomino L, Pellegrino M, Rago V, Mauro L, Lanzino M, et al: Activated FXR inhibits leptin signaling and counteracts tumor-promoting activities of cancer-associated fibroblasts in breast malignancy. Sci Rep. 6:217822016. View Article : Google Scholar : PubMed/NCBI | |
|
Strauss P, Rivedal M, Scherer A, Eikrem Ø, Nakken S, Beisland C, Bostad L, Flatberg A, Skandalou E, Beisvåg V, et al: A multiomics disease progression signature of low-risk ccRCC. Sci Rep. 12:135032022. View Article : Google Scholar : PubMed/NCBI | |
|
Fujino T, Sakamaki R, Ito H, Furusato Y, Sakamoto N, Oshima T and Hayakawa M: Farnesoid X receptor regulates the growth of renal adenocarcinoma cells without affecting that of a normal renal cell-derived cell line. J Toxicol Sci. 42:259–265. 2017. View Article : Google Scholar : PubMed/NCBI | |
|
Huang S, Hou Y, Hu M, Hu J and Liu X: Clinical significance and oncogenic function of NR1H4 in clear cell renal cell carcinoma. BMC Cancer. 22:9952022. View Article : Google Scholar : PubMed/NCBI | |
|
Tan SK, Hougen HY, Merchan JR, Gonzalgo ML and Welford SM: Fatty acid metabolism reprogramming in ccRCC: Mechanisms and potential targets. Nat Rev Urol. 20:48–60. 2023. View Article : Google Scholar | |
|
Zhang CJ, Zhu N, Wang YX, Liu LP, Zhao TJ, Wu HT, Liao DF and Qin L: Celastrol attenuates lipid accumulation and stemness of clear cell renal cell carcinoma via CAV-1/LOX-1 pathway. Front Pharmacol. 12:6580922021. View Article : Google Scholar : PubMed/NCBI | |
|
Xu GH, Lou N, Shi HC, Xu YC, Ruan HL, Xiao W, Liu L, Li X, Xiao HB, Qiu B, et al: Up-regulation of SR-BI promotes progression and serves as a prognostic biomarker in clear cell renal cell carcinoma. BMC Cancer. 18:882018. View Article : Google Scholar : PubMed/NCBI | |
|
Riscal R, Bull CJ, Mesaros C, Finan JM, Carens M, Ho ES, Xu JP, Godfrey J, Brennan P, Johansson M, et al: Cholesterol auxotrophy as a targetable vulnerability in clear cell renal cell carcinoma. Cancer Discov. 11:3106–3125. 2021. View Article : Google Scholar : PubMed/NCBI | |
|
Chao F, Gong W, Zheng Y, Li Y, Huang G, Gao M, Li J, Kuruba R, Gao X, Li S and He F: Upregulation of scavenger receptor class B type I expression by activation of FXR in hepatocyte. Atherosclerosis. 213:443–448. 2010. View Article : Google Scholar : PubMed/NCBI | |
|
Cariello M, Ducheix S, Maqdasy S, Baron S, Moschetta A and Lobaccaro JA: LXRs, SHP, and FXR in prostate cancer: Enemies or ménage à quatre with AR? Nucl Recept Signal. 15:15507629188010702018. View Article : Google Scholar | |
|
Liu J, Tong SJ, Wang X and Qu LX: Farnesoid X receptor inhibits LNcaP cell proliferation via the upregulation of PTEN. Exp Ther Med. 8:1209–1212. 2014. View Article : Google Scholar : PubMed/NCBI | |
|
Liu N, Zhao J, Wang J, Teng H, Fu Y and Yuan H: Farnesoid X receptor ligand CDCA suppresses human prostate cancer cells growth by inhibiting lipid metabolism via targeting sterol response element binding protein 1. Am J Transl Res. 8:5118–5124. 2016.PubMed/NCBI | |
|
Urizar NL, Liverman AB, Dodds DT, Silva FV, Ordentlich P, Yan Y, Gonzalez FJ, Heyman RA, Mangelsdorf DJ and Moore DD: A natural product that lowers cholesterol as an antagonist ligand for FXR. Science. 296:1703–1706. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Burris TP, Montrose C, Houck KA, Osborne HE, Bocchinfuso WP, Yaden BC, Cheng CC, Zink RW, Barr RJ, Hepler CD, et al: The hypolipidemic natural product guggulsterone is a promiscuous steroid receptor ligand. Mol Pharmacol. 67:948–954. 2005. View Article : Google Scholar | |
|
Bijsmans IT, Guercini C, Ramos Pittol JM, Omta W, Milona A, Lelieveld D, Egan DA, Pellicciari R, Gioiello A and van Mil SW: The glucocorticoid mometasone furoate is a novel FXR ligand that decreases inflammatory but not metabolic gene expression. Sci Rep. 5:140862015. View Article : Google Scholar : PubMed/NCBI | |
|
Dussault I, Beard R, Lin M, Hollister K, Chen J, Xiao JH, Chandraratna R and Forman BM: Identification of gene-selective modulators of the bile acid receptor FXR. J Biol Chem. 278:7027–7033. 2003. View Article : Google Scholar | |
|
Chang Y, Lin TY, Lu CW, Huang SK, Wang YC and Wang SJ: Xanthohumol-induced presynaptic reduction of glutamate release in the rat hippocampus. Food Funct. 7:212–226. 2016. View Article : Google Scholar | |
|
Liu W and Wong C: Oleanolic acid is a selective farnesoid X receptor modulator. Phytother Res. 24:369–373. 2010. View Article : Google Scholar | |
|
Fang S, Suh JM, Reilly SM, Yu E, Osborn O, Lackey D, Yoshihara E, Perino A, Jacinto S, Lukasheva Y, et al: Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med. 21:159–165. 2015. View Article : Google Scholar : PubMed/NCBI | |
|
Pellicciari R, Passeri D, De Franco F, Mostarda S, Filipponi P, Colliva C, Gadaleta RM, Franco P, Carotti A, Macchiarulo A, et al: Discovery of 3α,7α,11β-Trihydroxy-6α-ethyl-5β-cholan-2 4-oic Acid (TC-100), a novel bile acid as potent and highly selective FXR agonist for enterohepatic disorders. J Med Chem. 59:9201–9214. 2016. View Article : Google Scholar : PubMed/NCBI | |
|
Jin L, Wang R, Zhu Y, Zheng W, Han Y, Guo F, Ye FB and Li Y: Selective targeting of nuclear receptor FXR by avermectin analogues with therapeutic effects on nonalcoholic fatty liver disease. Sci Rep. 5:172882015. View Article : Google Scholar : PubMed/NCBI | |
|
Li G, Lin W, Araya JJ, Chen T, Timmermann BN and Guo GL: A tea catechin, epigallocatechin-3-gallate, is a unique modulator of the farnesoid X receptor. Toxicol Appl Pharmacol. 258:268–274. 2012. View Article : Google Scholar : |
