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Disturbed bile acid (BA) homeostasis and microcholestasis via hepatocellular retention of potentially toxic BAs may be an underappreciated factor in the pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) as its progressive variant. In addition to their detergent properties, BAs act as signaling molecules regulating cellular homeostasis through interaction with BA receptors such as the Farnesoid X receptor (FXR). Apart from being a key regulator of BA metabolism and enterohepatic circulation, FXR regulates metabolic homeostasis and has immune-modulatory effects, making it an attractive therapeutic target in NAFLD\/NASH. In this review, the molecular basis and therapeutic potential of targeting FXR with a specific focus on restoring BA and metabolic homeostasis in NASH is summarized.<\/jats:p>","DOI":"10.1055\/s-0041-1731707","type":"journal-article","created":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T22:57:53Z","timestamp":1626908273000},"page":"461-475","source":"Crossref","is-referenced-by-count":74,"title":["Role of FXR in Bile Acid and Metabolic Homeostasis in NASH: Pathogenetic Concepts and Therapeutic Opportunities"],"prefix":"10.1055","volume":"41","author":[{"given":"Richard","family":"Radun","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Hans Popper Laboratory of Molecular Hepatology, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Trauner","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Hans 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Chalasani","year":"2018","journal-title":"Hepatology"},{"issue":"01","key":"ref3","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1111\/jgh.13857","article-title":"Asia-Pacific Working Party on Non-alcoholic Fatty Liver Disease guidelines 2017-part 1: definition, risk factors and assessment","volume":"33","author":"V W-S Wong","year":"2018","journal-title":"J Gastroenterol Hepatol"},{"issue":"03","key":"ref4","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.jhep.2018.10.033","article-title":"Non-alcoholic fatty liver disease - a global public health perspective","volume":"70","author":"Z M Younossi","year":"2019","journal-title":"J Hepatol"},{"issue":"06","key":"ref5","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1002\/hep.30251","article-title":"Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis","volume":"69","author":"Z Younossi","year":"2019","journal-title":"Hepatology"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"15080","DOI":"10.1038\/nrdp.2015.80","article-title":"Nonalcoholic fatty liver disease","volume":"1","author":"E M Brunt","year":"2015","journal-title":"Nat Rev Dis Primers"},{"issue":"04","key":"ref7","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s11901-017-0378-2","article-title":"Natural history of NAFLD\/NASH","volume":"16","author":"M Ekstedt","year":"2017","journal-title":"Curr Hepatol Rep"},{"issue":"03","key":"ref8","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1055\/s-0035-1562943","article-title":"Epidemiology and natural history of nonalcoholic fatty liver disease","volume":"35","author":"S K Satapathy","year":"2015","journal-title":"Semin Liver Dis"},{"issue":"03","key":"ref9","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1055\/s-0035-1562944","article-title":"Systemic complications of nonalcoholic fatty liver disease: when the liver is not an innocent bystander","volume":"35","author":"E Vanni","year":"2015","journal-title":"Semin Liver Dis"},{"issue":"01","key":"ref10","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: an international expert consensus statement","volume":"73","author":"M Eslam","year":"2020","journal-title":"J Hepatol"},{"issue":"07","key":"ref11","doi-asserted-by":"crossref","first-page":"1999.e1","DOI":"10.1053\/j.gastro.2019.11.312","article-title":"MAFLD: a consensus-driven proposed nomenclature for metabolic associated fatty liver disease","volume":"158","author":"M Eslam","year":"2020","journal-title":"Gastroenterology"},{"issue":"06","key":"ref12","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1136\/gutjnl-2017-313884","article-title":"Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extrahepatic diseases","volume":"66","author":"L A Adams","year":"2017","journal-title":"Gut"},{"issue":"05","key":"ref13","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1136\/gutjnl-2020-322572","article-title":"Non-alcoholic fatty liver disease and risk of incident diabetes mellitus: an updated meta-analysis of 501 022 adult individuals","volume":"70","author":"A Mantovani","year":"2021","journal-title":"Gut"},{"issue":"06","key":"ref14","doi-asserted-by":"crossref","first-page":"1904","DOI":"10.1002\/hep.22868","article-title":"Quality of life in adults with nonalcoholic fatty liver disease: baseline data from the nonalcoholic steatohepatitis clinical research network","volume":"49","author":"K David","year":"2009","journal-title":"Hepatology"},{"issue":"06","key":"ref15","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1136\/gut.2007.139303","article-title":"Fatigue in non-alcoholic fatty liver disease (NAFLD) is significant and associates with inactivity and excessive daytime sleepiness but not with liver disease severity or insulin resistance","volume":"57","author":"J L Newton","year":"2008","journal-title":"Gut"},{"issue":"11","key":"ref16","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1002\/hep4.1581","article-title":"Fatigue and pruritus in patients with advanced fibrosis due to nonalcoholic steatohepatitis: the impact on patient-reported outcomes","volume":"4","author":"Z M Younossi","year":"2020","journal-title":"Hepatol Commun"},{"issue":"03","key":"ref17","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1053\/j.gastro.2014.11.039","article-title":"Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States","volume":"148","author":"R J Wong","year":"2015","journal-title":"Gastroenterology"},{"issue":"06","key":"ref18","doi-asserted-by":"crossref","first-page":"100192","DOI":"10.1016\/j.jhepr.2020.100192","article-title":"NAFLD and liver transplantation: disease burden, current management and future challenges","volume":"2","author":"P Burra","year":"2020","journal-title":"JHEP Rep"},{"issue":"05","key":"ref19","doi-asserted-by":"crossref","first-page":"1090.e1","DOI":"10.1053\/j.gastro.2017.01.003","article-title":"Changes in the prevalence of hepatitis C virus infection, nonalcoholic steatohepatitis, and alcoholic liver disease among patients with cirrhosis or liver failure on the waitlist for liver transplantation","volume":"152","author":"D Goldberg","year":"2017","journal-title":"Gastroenterology"},{"issue":"03","key":"ref20","doi-asserted-by":"crossref","first-page":"580.e5","DOI":"10.1016\/j.cgh.2020.05.064","article-title":"Nonalcoholic steatohepatitis is the most rapidly increasing indication for liver transplantation in the United States","volume":"19","author":"Z M Younossi","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"11","key":"ref21","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.1111\/liv.13751","article-title":"Nonalcoholic fatty liver disease is an increasing indication for liver transplantation in the Nordic countries","volume":"38","author":"M Holmer","year":"2018","journal-title":"Liver Int"},{"issue":"11","key":"ref22","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1016\/j.bcp.2013.08.015","article-title":"Bile acid receptors in non-alcoholic fatty liver disease","volume":"86","author":"Y Li","year":"2013","journal-title":"Biochem Pharmacol"},{"issue":"28","key":"ref23","doi-asserted-by":"crossref","first-page":"2811","DOI":"10.4254\/wjh.v7.i28.2811","article-title":"Bile acid receptors and nonalcoholic fatty liver disease","volume":"7","author":"L Yuan","year":"2015","journal-title":"World J Hepatol"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1002\/hep.28709","article-title":"Bile acids and nonalcoholic fatty liver disease: molecular insights and therapeutic perspectives","volume":"65","author":"J P Arab","year":"2017","journal-title":"Hepatology"},{"issue":"01","key":"ref25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrgastro.2013.151","article-title":"Bile acid receptors as targets for drug development","volume":"11","author":"F G Schaap","year":"2014","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev-pathol-020117-043617","article-title":"Recent insights into the pathogenesis of nonalcoholic fatty liver disease","volume":"13","author":"J P Arab","year":"2018","journal-title":"Annu Rev Pathol"},{"issue":"04","key":"ref27","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1002\/hep.28991","article-title":"New therapeutic concepts in bile acid transport and signaling for management of cholestasis","volume":"65","author":"M Trauner","year":"2017","journal-title":"Hepatology"},{"issue":"22","key":"ref28","doi-asserted-by":"crossref","first-page":"2647","DOI":"10.1001\/archinte.159.22.2647","article-title":"The continuing importance of bile acids in liver and intestinal disease","volume":"159","author":"A F Hofmann","year":"1999","journal-title":"Arch Intern Med"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.2741\/3399","article-title":"The enterohepatic circulation of bile acids in mammals: form and functions","volume":"14","author":"A F Hofmann","year":"2009","journal-title":"Front Biosci"},{"issue":"02","key":"ref30","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1002\/hep.28965","article-title":"The ascending pathophysiology of cholestatic liver disease","volume":"65","author":"P LM Jansen","year":"2017","journal-title":"Hepatology"},{"issue":"01","key":"ref31","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ajpath.2010.11.026","article-title":"Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis","volume":"178","author":"K Allen","year":"2011","journal-title":"Am J Pathol"},{"issue":"06","key":"ref32","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/j.jhep.2017.02.026","article-title":"Targeting hepatic macrophages to treat liver diseases","volume":"66","author":"F Tacke","year":"2017","journal-title":"J Hepatol"},{"issue":"04","key":"ref33","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1124\/pr.113.008201","article-title":"Bile acid signaling in metabolic disease and drug therapy","volume":"66","author":"T Li","year":"2014","journal-title":"Pharmacol Rev"},{"issue":"03","key":"ref34","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1002\/cphy.c120023","article-title":"Bile acid metabolism and signaling","volume":"3","author":"J YL Chiang","year":"2013","journal-title":"Compr Physiol"},{"key":"ref35","first-page":"25","article-title":"Bile acids in regulation of inflammation and immunity: friend or foe?","volume":"34","author":"C Zhu","year":"2016","journal-title":"Clin Exp Rheumatol"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"1362","DOI":"10.1126\/science.284.5418.1362","article-title":"Identification of a nuclear receptor for bile acids","volume":"284","author":"M Makishima","year":"1999","journal-title":"Science"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"1365","DOI":"10.1126\/science.284.5418.1365","article-title":"Bile acids: natural ligands for an orphan nuclear receptor","volume":"284","author":"D J Parks","year":"1999","journal-title":"Science"},{"issue":"05","key":"ref38","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/S1097-2765(00)80348-2","article-title":"Endogenous bile acids are ligands for the nuclear receptor FXR\/BAR","volume":"3","author":"H Wang","year":"1999","journal-title":"Mol Cell"},{"issue":"01","key":"ref39","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1002\/hep.24681","article-title":"Conjugated bile acids activate the sphingosine-1-phosphate receptor 2 in primary rodent hepatocytes","volume":"55","author":"E Studer","year":"2012","journal-title":"Hepatology"},{"issue":"03","key":"ref40","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S1097-2765(00)00051-4","article-title":"A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis","volume":"6","author":"B Goodwin","year":"2000","journal-title":"Mol Cell"},{"issue":"51","key":"ref41","doi-asserted-by":"crossref","first-page":"51085","DOI":"10.1074\/jbc.M308321200","article-title":"Farnesoid X receptor activates transcription of the phospholipid pump MDR3","volume":"278","author":"L Huang","year":"2003","journal-title":"J Biol Chem"},{"issue":"31","key":"ref42","doi-asserted-by":"crossref","first-page":"28857","DOI":"10.1074\/jbc.M011610200","article-title":"Human bile salt export pump promoter is transactivated by the farnesoid X receptor\/bile acid receptor","volume":"276","author":"M Ananthanarayanan","year":"2001","journal-title":"J Biol Chem"},{"issue":"01","key":"ref43","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1053\/gast.2001.25503","article-title":"The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp","volume":"121","author":"L A Denson","year":"2001","journal-title":"Gastroenterology"},{"issue":"03","key":"ref44","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S1097-2765(00)00050-2","article-title":"Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors","volume":"6","author":"T T Lu","year":"2000","journal-title":"Mol Cell"},{"issue":"01","key":"ref45","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/hep.20295","article-title":"Bile acid-induced negative feedback regulation of the human ileal bile acid transporter","volume":"40","author":"E Neimark","year":"2004","journal-title":"Hepatology"},{"issue":"01","key":"ref46","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/hep.22627","article-title":"Bile acids activate fibroblast growth factor 19 signaling in human hepatocytes to inhibit cholesterol 7alpha-hydroxylase gene expression","volume":"49","author":"K-H Song","year":"2009","journal-title":"Hepatology"},{"issue":"07","key":"ref47","doi-asserted-by":"crossref","first-page":"1679.e3","DOI":"10.1053\/j.gastro.2017.01.055","article-title":"Bile acid control of metabolism and inflammation in obesity, type 2 diabetes, dyslipidemia, and nonalcoholic fatty liver disease","volume":"152","author":"O Ch\u00e1vez-Talavera","year":"2017","journal-title":"Gastroenterology"},{"issue":"06","key":"ref48","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/S0092-8674(00)00062-3","article-title":"Targeted disruption of the nuclear receptor FXR\/BAR impairs bile acid and lipid homeostasis","volume":"102","author":"C J Sinal","year":"2000","journal-title":"Cell"},{"issue":"04","key":"ref49","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1073\/pnas.0506982103","article-title":"Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice","volume":"103","author":"Y Zhang","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"ref50","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.1172\/JCI21025","article-title":"Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c","volume":"113","author":"M Watanabe","year":"2004","journal-title":"J Clin Invest"},{"issue":"01","key":"ref51","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1055\/s-0036-1571296","article-title":"Nuclear receptor modulation for the treatment of nonalcoholic fatty liver disease","volume":"36","author":"C D Fuchs","year":"2016","journal-title":"Semin Liver Dis"},{"issue":"02","key":"ref52","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1210\/me.2002-0120","article-title":"Bile acids induce the expression of the human peroxisome proliferator-activated receptor alpha gene via activation of the farnesoid X receptor","volume":"17","author":"I Pineda Torra","year":"2003","journal-title":"Mol Endocrinol"},{"issue":"06","key":"ref53","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1016\/j.cmet.2011.03.019","article-title":"FGF15\/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1\u03b1 pathway","volume":"13","author":"M J Potthoff","year":"2011","journal-title":"Cell Metab"},{"issue":"10","key":"ref54","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1002\/j.1552-4604.1981.tb01746.x","article-title":"Chenodeoxycholic acid and ursodeoxycholic acid effects in endogenous hypertriglyceridemias. A controlled double-blind trial","volume":"21","author":"N Carulli","year":"1981","journal-title":"J Clin Pharmacol"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1001\/jama.1965.03080170017004","article-title":"Cholestyramine resin therapy for hypercholesteremia: clinical and metabolic studies","volume":"192","author":"S A Hashim","year":"1965","journal-title":"JAMA"},{"issue":"06","key":"ref56","doi-asserted-by":"crossref","first-page":"416","DOI":"10.7326\/0003-4819-121-6-199409150-00004","article-title":"Cholestyramine therapy for dyslipidemia in non-insulin-dependent diabetes mellitus. A short-term, double-blind, crossover trial","volume":"121","author":"A Garg","year":"1994","journal-title":"Ann Intern Med"},{"issue":"02","key":"ref57","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1016\/0002-9343(87)90692-9","article-title":"Hypertriglyceridemia: a contraindication to the use of bile acid binding resins","volume":"83","author":"J R Crouse III","year":"1987","journal-title":"Am J Med"},{"issue":"04","key":"ref58","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1172\/JCI25604","article-title":"Farnesoid X receptor is essential for normal glucose homeostasis","volume":"116","author":"K Ma","year":"2006","journal-title":"J Clin Invest"},{"issue":"04","key":"ref59","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1194\/jlr.M001602","article-title":"FXR activation reverses insulin resistance and lipid abnormalities and protects against liver steatosis in Zucker (fa\/fa) obese rats","volume":"51","author":"S Cipriani","year":"2010","journal-title":"J Lipid Res"},{"issue":"09","key":"ref60","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1007\/s00018-014-1805-y","article-title":"Nuclear bile acid signaling through the farnesoid X receptor","volume":"72","author":"C Mazuy","year":"2015","journal-title":"Cell Mol Life Sci"},{"issue":"01","key":"ref61","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1007\/s11892-009-0087-5","article-title":"Bile acid sequestrants for lipid and glucose control","volume":"10","author":"B Staels","year":"2010","journal-title":"Curr Diab Rep"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1126\/science.1198363","article-title":"FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis","volume":"331","author":"S Kir","year":"2011","journal-title":"Science"},{"issue":"05","key":"ref63","doi-asserted-by":"crossref","first-page":"1632","DOI":"10.1002\/hep.22519","article-title":"Farnesoid X receptor antagonizes nuclear factor kappaB in hepatic inflammatory response","volume":"48","author":"Y-D Wang","year":"2008","journal-title":"Hepatology"},{"issue":"17","key":"ref64","doi-asserted-by":"crossref","first-page":"11761","DOI":"10.1074\/jbc.M112.446575","article-title":"Bile acid receptor activation modulates hepatic monocyte activity and improves nonalcoholic fatty liver disease","volume":"288","author":"R H McMahan","year":"2013","journal-title":"J Biol Chem"},{"issue":"06","key":"ref65","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.2353\/ajpath.2009.090114","article-title":"Farnesoid X receptor critically determines the fibrotic response in mice but is expressed to a low extent in human hepatic stellate cells and periductal myofibroblasts","volume":"175","author":"P Fickert","year":"2009","journal-title":"Am J Pathol"},{"issue":"06","key":"ref66","doi-asserted-by":"crossref","first-page":"2286","DOI":"10.1002\/hep.26939","article-title":"Obeticholic acid, a farnesoid X receptor agonist, improves portal hypertension by two distinct pathways in cirrhotic rats","volume":"59","author":"L Verbeke","year":"2014","journal-title":"Hepatology"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"33453","DOI":"10.1038\/srep33453","article-title":"FXR agonist obeticholic acid reduces hepatic inflammation and fibrosis in a rat model of toxic cirrhosis","volume":"6","author":"L Verbeke","year":"2016","journal-title":"Sci Rep"},{"issue":"02","key":"ref68","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1053\/j.gastro.2006.12.041","article-title":"Nitroflurbiprofen, a nitric oxide-releasing cyclooxygenase inhibitor, improves cirrhotic portal hypertension in rats","volume":"132","author":"W Laleman","year":"2007","journal-title":"Gastroenterology"},{"issue":"04","key":"ref69","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.jhep.2016.12.005","article-title":"The FXR agonist PX20606 ameliorates portal hypertension by targeting vascular remodelling and sinusoidal dysfunction","volume":"66","author":"P Schwabl","year":"2017","journal-title":"J Hepatol"},{"issue":"01","key":"ref70","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/s41467-019-14138-6","article-title":"SUMOylation inhibitors synergize with FXR agonists in combating liver fibrosis","volume":"11","author":"J Zhou","year":"2020","journal-title":"Nat Commun"},{"issue":"04","key":"ref71","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.femsre.2004.09.003","article-title":"The interaction between bacteria and bile","volume":"29","author":"M Begley","year":"2005","journal-title":"FEMS Microbiol Rev"},{"issue":"03","key":"ref72","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1097\/MOG.0000000000000057","article-title":"Bile acids and the gut microbiome","volume":"30","author":"J M Ridlon","year":"2014","journal-title":"Curr Opin Gastroenterol"},{"issue":"10","key":"ref73","doi-asserted-by":"crossref","first-page":"3920","DOI":"10.1073\/pnas.0509592103","article-title":"Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor","volume":"103","author":"T Inagaki","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"03","key":"ref74","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1053\/jhep.2003.50116","article-title":"Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats","volume":"37","author":"V Lorenzo-Z\u00fa\u00f1iga","year":"2003","journal-title":"Hepatology"},{"issue":"02","key":"ref75","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1016\/j.ajpath.2014.10.009","article-title":"The FXR agonist obeticholic acid prevents gut barrier dysfunction and bacterial translocation in cholestatic rats","volume":"185","author":"L Verbeke","year":"2015","journal-title":"Am J Pathol"},{"issue":"04","key":"ref76","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1136\/gut.2010.212159","article-title":"Farnesoid X receptor activation inhibits inflammation and preserves the intestinal barrier in inflammatory bowel disease","volume":"60","author":"R M Gadaleta","year":"2011","journal-title":"Gut"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41586-020-2193-0","article-title":"Bacterial metabolism of bile acids promotes generation of peripheral regulatory T cells","volume":"581","author":"C Campbell","year":"2020","journal-title":"Nature"},{"issue":"05","key":"ref78","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1053\/j.gastro.2016.08.057","article-title":"An intestinal microbiota-farnesoid X receptor axis modulates metabolic disease","volume":"151","author":"F J Gonzalez","year":"2016","journal-title":"Gastroenterology"},{"issue":"02","key":"ref79","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1038\/nrgastro.2017.119","article-title":"Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis","volume":"15","author":"W Jia","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"02","key":"ref80","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.cmet.2013.01.003","article-title":"Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist","volume":"17","author":"S I Sayin","year":"2013","journal-title":"Cell Metab"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"2384","DOI":"10.1038\/ncomms3384","article-title":"Microbiome remodelling leads to inhibition of intestinal farnesoid X receptor signalling and decreased obesity","volume":"4","author":"F Li","year":"2013","journal-title":"Nat Commun"},{"issue":"08","key":"ref82","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.tem.2012.04.005","article-title":"Role of ceramides in nonalcoholic fatty liver disease","volume":"23","author":"M Pagadala","year":"2012","journal-title":"Trends Endocrinol Metab"},{"issue":"01","key":"ref83","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1172\/JCI76738","article-title":"Intestinal farnesoid X receptor signaling promotes nonalcoholic fatty liver disease","volume":"125","author":"C Jiang","year":"2015","journal-title":"J Clin Invest"},{"issue":"03","key":"ref84","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1136\/gutjnl-2015-310283","article-title":"Microbiota-induced obesity requires farnesoid X receptor","volume":"66","author":"A Pars\u00e9us","year":"2017","journal-title":"Gut"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"1241214","DOI":"10.1126\/science.1241214","article-title":"Gut microbiota from twins discordant for obesity modulate metabolism in mice","volume":"341","author":"V K Ridaura","year":"2013","journal-title":"Science"},{"issue":"10","key":"ref86","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1136\/gutjnl-2017-314307","article-title":"Suppressed hepatic bile acid signalling despite elevated production of primary and secondary bile acids in NAFLD","volume":"67","author":"N Jiao","year":"2018","journal-title":"Gut"},{"issue":"02","key":"ref87","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1002\/hep.29359","article-title":"The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids","volume":"67","author":"P Puri","year":"2018","journal-title":"Hepatology"},{"issue":"04","key":"ref88","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1002\/hep.26225","article-title":"Free fatty acids repress small heterodimer partner (SHP) activation and adiponectin counteracts bile acid-induced liver injury in superobese patients with nonalcoholic steatohepatitis","volume":"57","author":"L P Bechmann","year":"2013","journal-title":"Hepatology"},{"issue":"11","key":"ref89","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1007\/s10620-015-3776-8","article-title":"Altered bile acid metabolome in patients with nonalcoholic steatohepatitis","volume":"60","author":"B C Ferslew","year":"2015","journal-title":"Dig Dis Sci"},{"issue":"05","key":"ref90","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1097\/MEG.0b013e328345c8c7","article-title":"Elevated hepatic fatty acid oxidation, high plasma fibroblast growth factor 21, and fasting bile acids in nonalcoholic steatohepatitis","volume":"23","author":"S Dasarathy","year":"2011","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"05","key":"ref91","doi-asserted-by":"crossref","first-page":"e0151829","DOI":"10.1371\/journal.pone.0151829","article-title":"Bile acids and dysbiosis in non-alcoholic fatty liver disease","volume":"11","author":"M Mouzaki","year":"2016","journal-title":"PLoS One"},{"issue":"03","key":"ref92","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.metabol.2010.03.006","article-title":"Plasma metabolomic profile in nonalcoholic fatty liver disease","volume":"60","author":"S C Kalhan","year":"2011","journal-title":"Metabolism"},{"issue":"06","key":"ref93","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1097\/MEG.0b013e3282f4710a","article-title":"Bile acid levels are increased in the liver of patients with steatohepatitis","volume":"20","author":"M M Aranha","year":"2008","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"10","key":"ref94","doi-asserted-by":"crossref","first-page":"3783","DOI":"10.1210\/jc.2017-01397","article-title":"Bile acid alterations are associated with insulin resistance, but not with NASH, in obese subjects","volume":"102","author":"V Legry","year":"2017","journal-title":"J Clin Endocrinol Metab"},{"issue":"12","key":"ref95","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.2337\/db13-0639","article-title":"Human insulin resistance is associated with increased plasma levels of 12\u03b1-hydroxylated bile acids","volume":"62","author":"R A Haeusler","year":"2013","journal-title":"Diabetes"},{"issue":"01","key":"ref96","first-page":"1","article-title":"Diabetes mellitus-induced alterations of hepatobiliary function","volume":"47","author":"J B Watkins III","year":"1995","journal-title":"Pharmacol Rev"},{"issue":"02","key":"ref97","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1002\/hep.1840080224","article-title":"Diabetes-induced cholestasis in the rat: possible role of hyperglycemia and hypoinsulinemia","volume":"8","author":"J J Garcia-Marin","year":"1988","journal-title":"Hepatology"},{"issue":"03","key":"ref98","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/0300-483X(91)90070-H","article-title":"Studies on the mechanism of bile salt-independent bile flow impairment in streptozotocin-induced hepatotoxicity","volume":"68","author":"C E Carnovale","year":"1991","journal-title":"Toxicology"},{"issue":"02","key":"ref99","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1002\/hep.1840160222","article-title":"Spontaneously diabetic biobreeding rats and impairment of bile acid-independent bile flow and increased biliary bilirubin, calcium and lipid secretion","volume":"16","author":"J Gonz\u00e1lez","year":"1992","journal-title":"Hepatology"},{"issue":"01","key":"ref100","doi-asserted-by":"crossref","first-page":"17193","DOI":"10.1038\/s41598-017-17370-6","article-title":"The transcriptomic signature of disease development and progression of nonalcoholic fatty liver disease","volume":"7","author":"S Cazanave","year":"2017","journal-title":"Sci Rep"},{"issue":"05","key":"ref101","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1016\/j.cmet.2012.04.004","article-title":"Increased hepatic synthesis and dysregulation of cholesterol metabolism is associated with the severity of nonalcoholic fatty liver disease","volume":"15","author":"H-K Min","year":"2012","journal-title":"Cell Metab"},{"issue":"02","key":"ref102","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1111\/liv.13531","article-title":"Hepatic farnesoid X receptor protein level and circulating fibroblast growth factor 19 concentration in children with NAFLD","volume":"38","author":"V Nobili","year":"2018","journal-title":"Liver Int"},{"issue":"09","key":"ref103","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.clinbiochem.2012.03.019","article-title":"Preliminary evidence of a reduced serum level of fibroblast growth factor 19 in patients with biopsy-proven nonalcoholic fatty liver disease","volume":"45","author":"F Eren","year":"2012","journal-title":"Clin Biochem"},{"issue":"03","key":"ref104","doi-asserted-by":"crossref","first-page":"G440","DOI":"10.1152\/ajpgi.00322.2009","article-title":"The hepatic response to FGF19 is impaired in patients with nonalcoholic fatty liver disease and insulin resistance","volume":"298","author":"T CMA Schreuder","year":"2010","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"06","key":"ref105","doi-asserted-by":"crossref","first-page":"e67160","DOI":"10.1371\/journal.pone.0067160","article-title":"Association between serum atypical fibroblast growth factors 21 and 19 and pediatric nonalcoholic fatty liver disease","volume":"8","author":"A Alisi","year":"2013","journal-title":"PLoS One"},{"issue":"03","key":"ref106","doi-asserted-by":"crossref","first-page":"e00131","DOI":"10.14309\/ctg.0000000000000131","article-title":"Altered microbiota diversity and bile acid signaling in cirrhotic and noncirrhotic NASH-HCC","volume":"11","author":"S Sydor","year":"2020","journal-title":"Clin Transl Gastroenterol"},{"issue":"01","key":"ref107","doi-asserted-by":"crossref","first-page":"e0211348","DOI":"10.1371\/journal.pone.0211348","article-title":"Non-alcoholic fatty liver disease is associated with dysregulated bile acid synthesis and diarrhea: a prospective observational study","volume":"14","author":"R N Appleby","year":"2019","journal-title":"PLoS One"},{"key":"ref108","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1038\/nature12347","article-title":"Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome","volume":"499","author":"S Yoshimoto","year":"2013","journal-title":"Nature"},{"issue":"06","key":"ref109","doi-asserted-by":"crossref","first-page":"2015","DOI":"10.1002\/hep.28829","article-title":"Changes in blood microbiota profiles associated with liver fibrosis in obese patients: a pilot analysis","volume":"64","author":"B Lelouvier","year":"2016","journal-title":"Hepatology"},{"issue":"04","key":"ref110","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1053\/gast.2002.35948","article-title":"Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles","volume":"123","author":"P Fickert","year":"2002","journal-title":"Gastroenterology"},{"issue":"04","key":"ref111","doi-asserted-by":"crossref","first-page":"G725","DOI":"10.1152\/ajpgi.90265.2008","article-title":"Cholangiocyte primary cilia are chemosensory organelles that detect biliary nucleotides via P2Y12 purinergic receptors","volume":"295","author":"A I Masyuk","year":"2008","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"12","key":"ref112","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1038\/s41591-019-0660-7","article-title":"Three-dimensional spatially resolved geometrical and functional models of human liver tissue reveal new aspects of NAFLD progression","volume":"25","author":"F Segovia-Miranda","year":"2019","journal-title":"Nat Med"},{"issue":"12","key":"ref113","doi-asserted-by":"crossref","first-page":"1837","DOI":"10.1136\/gut.2003.037689","article-title":"Bile secretory function in the obese Zucker rat: evidence of cholestasis and altered canalicular transport function","volume":"53","author":"M Pizarro","year":"2004","journal-title":"Gut"},{"issue":"06","key":"ref114","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1016\/j.jhep.2005.05.031","article-title":"Characterization of organic anion transporter regulation, glutathione metabolism and bile formation in the obese Zucker rat","volume":"43","author":"A Geier","year":"2005","journal-title":"J Hepatol"},{"issue":"06","key":"ref115","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1124\/dmd.114.062703","article-title":"Altered regulation of hepatic efflux transporters disrupts acetaminophen disposition in pediatric nonalcoholic steatohepatitis","volume":"43","author":"M J Canet","year":"2015","journal-title":"Drug Metab Dispos"},{"issue":"03","key":"ref116","doi-asserted-by":"crossref","first-page":"e22035","DOI":"10.1002\/jbt.22035","article-title":"Misregulation of membrane trafficking processes in human nonalcoholic steatohepatitis","volume":"32","author":"A L Dzierlenga","year":"2018","journal-title":"J Biochem Mol Toxicol"},{"issue":"04","key":"ref117","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1002\/hep.22771","article-title":"High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis","volume":"49","author":"F G Schaap","year":"2009","journal-title":"Hepatology"},{"issue":"03","key":"ref118","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1053\/jhep.2001.22646","article-title":"Hepatobiliary transporter expression in percutaneous liver biopsies of patients with cholestatic liver diseases","volume":"33","author":"G Zollner","year":"2001","journal-title":"Hepatology"},{"issue":"29","key":"ref119","doi-asserted-by":"crossref","first-page":"24784","DOI":"10.1074\/jbc.M111.329318","article-title":"Abcb11 deficiency induces cholestasis coupled to impaired \u03b2-fatty acid oxidation in mice","volume":"287","author":"Y Zhang","year":"2012","journal-title":"J Biol Chem"},{"issue":"06","key":"ref120","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1111\/liv.14423","article-title":"Absence of Bsep\/Abcb11 attenuates MCD diet-induced hepatic steatosis but aggravates inflammation in mice","volume":"40","author":"C D Fuchs","year":"2020","journal-title":"Liver Int"},{"issue":"08","key":"ref121","doi-asserted-by":"crossref","first-page":"e0234750","DOI":"10.1371\/journal.pone.0234750","article-title":"Heterozygous knockout of Bile salt export pump ameliorates liver steatosis in mice fed a high-fat diet","volume":"15","author":"K Okushin","year":"2020","journal-title":"PLoS One"},{"issue":"09","key":"ref122","doi-asserted-by":"crossref","first-page":"s-0029","DOI":"10.1055\/s-0029-1241387","article-title":"The common bile salt export pump (ABCB11) p.A444V variant is associated with BMI levels in the general population","volume":"47","author":"M Krawczyk","year":"2009","journal-title":"Z Gastroenterol"},{"issue":"06","key":"ref123","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s11745-009-3300-z","article-title":"Common variants of ABCB4 and ABCB11 and plasma lipid levels: a study in sib pairs with gallstones, and controls","volume":"44","author":"M Acalovschi","year":"2009","journal-title":"Lipids"},{"issue":"02","key":"ref124","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1016\/j.jhep.2017.11.014","article-title":"Lipotoxicity and the gut-liver axis in NASH pathogenesis","volume":"68","author":"F Marra","year":"2018","journal-title":"J Hepatol"},{"issue":"04","key":"ref125","first-page":"500","article-title":"FXR agonists as therapeutic agents for non-alcoholic fatty liver disease","volume":"17","author":"R M Carr","year":"2015","journal-title":"Curr Atheroscler Rep"},{"issue":"01","key":"ref126","doi-asserted-by":"crossref","first-page":"8157","DOI":"10.1038\/s41598-018-26383-8","article-title":"Obeticholic acid protects against hepatocyte death and liver fibrosis in a murine model of nonalcoholic steatohepatitis","volume":"8","author":"T Goto","year":"2018","journal-title":"Sci Rep"},{"issue":"02","key":"ref127","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.jhep.2009.03.025","article-title":"Farnesoid X receptor agonist WAY-362450 attenuates liver inflammation and fibrosis in murine model of non-alcoholic steatohepatitis","volume":"51","author":"S Zhang","year":"2009","journal-title":"J Hepatol"},{"issue":"02","key":"ref128","doi-asserted-by":"crossref","first-page":"H272","DOI":"10.1152\/ajpheart.01075.2008","article-title":"Antiatherosclerotic effect of farnesoid X receptor","volume":"296","author":"A Mencarelli","year":"2009","journal-title":"Am J Physiol Heart Circ Physiol"},{"issue":"06","key":"ref129","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1194\/jlr.M800619-JLR200","article-title":"Activation of farnesoid X receptor prevents atherosclerotic lesion formation in LDLR-\/- and apoE-\/- mice","volume":"50","author":"H B Hartman","year":"2009","journal-title":"J Lipid Res"},{"issue":"03","key":"ref130","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1124\/jpet.112.196519","article-title":"Synthetic farnesoid X receptor agonists induce high-density lipoprotein-mediated transhepatic cholesterol efflux in mice and monkeys and prevent atherosclerosis in cholesteryl ester transfer protein transgenic low-density lipoprotein receptor (-\/-) mice","volume":"343","author":"E Hambruch","year":"2012","journal-title":"J Pharmacol Exp Ther"},{"issue":"12","key":"ref131","doi-asserted-by":"crossref","first-page":"2606","DOI":"10.1161\/ATVBAHA.107.152694","article-title":"Farnesoid x receptor ligands inhibit vascular smooth muscle cell inflammation and migration","volume":"27","author":"Y TY Li","year":"2007","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"05","key":"ref132","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1074\/jbc.M115.694323","article-title":"Farnesoid X receptor protects against kidney injury in uninephrectomized obese mice","volume":"291","author":"Z Gai","year":"2016","journal-title":"J Biol Chem"},{"issue":"07","key":"ref133","doi-asserted-by":"crossref","first-page":"E2069","DOI":"10.3390\/ijms19072069","article-title":"Update on FXR biology: promising therapeutic target?","volume":"19","author":"C Y Han","year":"2018","journal-title":"Int J Mol Sci"},{"key":"ref134","doi-asserted-by":"crossref","first-page":"1382","DOI":"10.3389\/fphar.2018.01382","article-title":"Pharmacological applications of bile acids and their derivatives in the treatment of metabolic syndrome","volume":"9","author":"M \u0110ani\u0107","year":"2018","journal-title":"Front Pharmacol"},{"issue":"03","key":"ref135","doi-asserted-by":"crossref","first-page":"574.e1","DOI":"10.1053\/j.gastro.2013.05.042","article-title":"Efficacy and safety of the farnesoid X receptor agonist obeticholic acid in patients with type 2 diabetes and nonalcoholic fatty liver disease","volume":"145","author":"S Mudaliar","year":"2013","journal-title":"Gastroenterology"},{"key":"ref136","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S0140-6736(14)61933-4","article-title":"Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial","volume":"385","author":"B A Neuschwander-Tetri","year":"2015","journal-title":"Lancet"},{"key":"ref137","doi-asserted-by":"crossref","first-page":"2184","DOI":"10.1016\/S0140-6736(19)33041-7","article-title":"Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial","volume":"394","author":"Z M Younossi","year":"2019","journal-title":"Lancet"},{"key":"ref138","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1007\/164_2019_232","article-title":"Nonsteroidal FXR ligands: current status and clinical applications","volume":"256","author":"C Gege","year":"2019","journal-title":"Handb Exp Pharmacol"},{"issue":"01","key":"ref139","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/hep.31205","article-title":"Cilofexor, a nonsteroidal FXR agonist, in patients with noncirrhotic NASH: a phase 2 randomized controlled trial","volume":"72","author":"K Patel","year":"2020","journal-title":"Hepatology"},{"issue":"02","key":"ref140","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1002\/hep.31622","article-title":"Combination therapies including cilofexor and firsocostat for bridging fibrosis and cirrhosis attributable to NASH","volume":"73","author":"R Loomba","year":"2021","journal-title":"Hepatology"},{"issue":"24","key":"ref141","doi-asserted-by":"crossref","first-page":"9960","DOI":"10.1021\/acs.jmedchem.7b00907","article-title":"Discovery of tropifexor (LJN452), a highly potent non-bile acid FXR agonist for the treatment of cholestatic liver diseases and nonalcoholic steatohepatitis (NASH)","volume":"60","author":"D C Tully","year":"2017","journal-title":"J Med Chem"},{"issue":"08","key":"ref142","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1002\/hep4.1368","article-title":"Tropifexor-mediated abrogation of steatohepatitis and fibrosis is associated with the antioxidative gene expression profile in rodents","volume":"3","author":"E D Hernandez","year":"2019","journal-title":"Hepatol Commun"},{"issue":"03","key":"ref143","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1002\/cpdd.762","article-title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of the novel non-bile acid FXR agonist tropifexor (LJN452) in healthy volunteers","volume":"9","author":"M K Badman","year":"2020","journal-title":"Clin Pharmacol Drug Dev"},{"issue":"01","key":"ref144","doi-asserted-by":"crossref","first-page":"E38","DOI":"10.1016\/j.dld.2019.12.129","article-title":"Tropifexor, a highly potent FXR agonist, produces robust and dose-dependent reductions in hepatic fat and serum alanine aminotransferase in patients with fibrotic NASH after 12 weeks of therapy: FLIGHT-FXR Part C interim results","volume":"52","author":"K J Lucas","year":"2020","journal-title":"Dig Liv Dis"},{"issue":"06","key":"ref145","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1194\/jlr.M081935","article-title":"FXR activation by obeticholic acid or nonsteroidal agonists induces a human-like lipoprotein cholesterol change in mice with humanized chimeric liver","volume":"59","author":"R Papazyan","year":"2018","journal-title":"J Lipid Res"},{"issue":"01","key":"ref146","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jhep.2017.03.022","article-title":"EASL Clinical Practice Guidelines: the diagnosis and management of patients with primary biliary cholangitis","volume":"67","author":"European Association for the Study of the Liver. Electronic address: easloffice@easloffice.eu","year":"2017","journal-title":"J Hepatol"},{"issue":"12","key":"ref147","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.1158\/0008-5472.CAN-14-0208","article-title":"Separating tumorigenicity from bile acid regulatory activity for endocrine hormone FGF19","volume":"74","author":"M Zhou","year":"2014","journal-title":"Cancer Res"},{"issue":"01","key":"ref148","doi-asserted-by":"crossref","first-page":"17210","DOI":"10.1038\/s41598-018-35496-z","article-title":"Suppression of hepatic bile acid synthesis by a non-tumorigenic FGF19 analogue protects mice from fibrosis and hepatocarcinogenesis","volume":"8","author":"R M Gadaleta","year":"2018","journal-title":"Sci Rep"},{"issue":"01","key":"ref149","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1002\/hep.31523","article-title":"The commensal microbe veillonella as a marker for response to an FGF19 analog in NASH","volume":"73","author":"R Loomba","year":"2021","journal-title":"Hepatology"},{"issue":"07","key":"ref150","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1038\/s41591-019-0485-4","article-title":"Meta-omics analysis of elite athletes identifies a performance-enhancing microbe that functions via lactate metabolism","volume":"25","author":"J Scheiman","year":"2019","journal-title":"Nat Med"},{"issue":"04","key":"ref151","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1002\/hep.30590","article-title":"NGM282 improves liver fibrosis and histology in 12 weeks in patients with nonalcoholic steatohepatitis","volume":"71","author":"S A Harrison","year":"2020","journal-title":"Hepatology"},{"issue":"01","key":"ref152","doi-asserted-by":"crossref","first-page":"219.e1","DOI":"10.1053\/j.gastro.2020.08.004","article-title":"Efficacy and safety of aldafermin, an engineered FGF19 analog, in a randomized, double-blind, placebo-controlled trial of patients with nonalcoholic steatohepatitis","volume":"160","author":"S A Harrison","year":"2021","journal-title":"Gastroenterology"},{"issue":"03","key":"ref153","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.jhep.2018.10.035","article-title":"Effect of NGM282, an FGF19 analogue, in primary sclerosing cholangitis: a multicenter, randomized, double-blind, placebo-controlled phase II trial","volume":"70","author":"G M Hirschfield","year":"2019","journal-title":"J Hepatol"},{"key":"ref154","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1016\/S0140-6736(18)30474-4","article-title":"NGM282 for treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial","volume":"391","author":"S A Harrison","year":"2018","journal-title":"Lancet"},{"issue":"04","key":"ref155","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/j.jhep.2018.11.032","article-title":"Rosuvastatin improves the FGF19 analogue NGM282-associated lipid 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