The Farnesoid X Receptor: Good for BAD

被引:51
作者
Keely, Stephen J. [1 ]
Walters, Julian R. F. [2 ]
机构
[1] Beaumont Hosp, Educ & Res Ctr, Royal Coll Surg Ireland, Mol Med Labs, Smurfit Bldg, Dublin 9, Ireland
[2] Imperial Coll London, Hammersmith Hosp, Div Digest Dis, London, England
来源
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY | 2016年 / 2卷 / 06期
基金
爱尔兰科学基金会;
关键词
Bile Acid Diarrhea; Enterohepatic Circulation; FGF-19; Chloride Secretion; Epithelium;
D O I
10.1016/j.jcmgh.2016.08.004
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Diarrhea is a feature of several chronic intestinal disorders that are associated with increased delivery of bile acids into the colon. Although the prevalence of bile acid diarrhea is high, affecting approximately 1% of the adult population, current therapies often are unsatisfactory. By virtue of its capacity to inhibit colonic epithelial fluid secretion and to down-regulate hepatic bile acid synthesis through induction of the ileal fibroblast growth factor 19 release, the nuclear bile acid receptor, farnesoid X receptor, represents a promising target for the development of new therapeutic approaches. Here, we review our current understanding of the pathophysiology of bile acid diarrhea and the current evidence supporting a role for farnesoid X receptor agonists in treatment of the disease.
引用
收藏
页码:725 / 732
页数:8
相关论文
共 70 条
[41]   Diarrhea in Crohn's Disease: Investigating the Role of the Ileal Hormone Fibroblast Growth Factor 19 [J].
Nolan, Jonathan D. ;
Johnston, Ian M. ;
Pattni, Sanjeev S. ;
Dew, Tracy ;
Orchard, Timothy R. ;
Walters, Julian R. F. .
JOURNAL OF CROHNS & COLITIS, 2015, 9 (02) :125-131
[42]  
OREKOYA O, 2015, CLIN MED, V15, P371
[43]   Antibody-Mediated Inhibition of Fibroblast Growth Factor 19 Results in Increased Bile Acids Synthesis and Ileal Malabsorption of Bile Acids in Cynomolgus Monkeys [J].
Pai, Rama ;
French, Dorothy ;
Ma, Ning ;
Hotzel, Kathy ;
Plise, Emile ;
Salphati, Laurent ;
Setchell, Kenneth D. R. ;
Ware, Joseph ;
Lauriault, Veronique ;
Schutt, Leah ;
Hartley, Dylan ;
Dambach, Donna .
TOXICOLOGICAL SCIENCES, 2012, 126 (02) :446-456
[44]   Bile acids inhibit Na+/H+ exchanger and Cl-/HCO3 - exchanger activities via cellular energy breakdown and Ca2+ overload in human colonic crypts [J].
Pallagi-Kunstar, E. ;
Farkas, K. ;
Maleth, J. ;
Rakonczay, Z. Jr Jr ;
Nagy, F. ;
Molnar, T. ;
Szepes, Z. ;
Venglovecz, V. ;
Lonovics, J. ;
Razga, Z. ;
Wittmann, T. ;
Hegyi, P. .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 2015, 467 (06) :1277-1290
[45]   Bile acids: Natural ligands for an orphan nuclear receptor [J].
Parks, DJ ;
Blanchard, SG ;
Bledsoe, RK ;
Chandra, G ;
Consler, TG ;
Kliewer, SA ;
Stimmel, JB ;
Willson, TM ;
Zavacki, AM ;
Moore, DD ;
Lehmann, JM .
SCIENCE, 1999, 284 (5418) :1365-1368
[46]   Fibroblast growth factor 19 in patients with bile acid diarrhoea: a prospective comparison of FGF19 serum assay and SeHCAT retention [J].
Pattni, S. S. ;
Brydon, W. G. ;
Dew, T. ;
Johnston, I. M. ;
Nolan, J. D. ;
Srinivas, M. ;
Basumani, P. ;
Bardhan, K. D. ;
Walters, J. R. F. .
ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2013, 38 (08) :967-976
[47]   6α-ethyl-chenodeoxycholic acid (6-ECDCA), a potent and selective FXR agonist endowed with anticholestatic activity [J].
Pellicciari, R ;
Fiorucci, S ;
Camaioni, E ;
Clerici, C ;
Costantino, G ;
Maloney, PR ;
Morelli, A ;
Parks, DJ ;
Willson, TM .
JOURNAL OF MEDICINAL CHEMISTRY, 2002, 45 (17) :3569-3572
[48]  
Reiberger T, 2016, Z GASTROENTEROL, V54, pV02
[49]   The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane X receptors [J].
Ricketts, Marie-Louise ;
Boekschoten, Mark V. ;
Kreeft, Arja J. ;
Hooiveld, Guido J. E. J. ;
Moen, Corina J. A. ;
Mueller, Michael ;
Frants, Rune R. ;
Kasanmoentalib, Soemini ;
Post, Sabine M. ;
Princen, Hans M. G. ;
Porter, J. Gordon ;
Katan, Martijn B. ;
Hofker, Marten H. ;
Moore, David D. .
MOLECULAR ENDOCRINOLOGY, 2007, 21 (07) :1603-1616
[50]   Functional Characterization of the Semisynthetic Bile Acid Derivative INT-767, a Dual Farnesoid X Receptor and TGR5 Agonist [J].
Rizzo, Giovanni ;
Passeri, Daniela ;
De Franco, Francesca ;
Ciaccioli, Gianmario ;
Donadio, Loredana ;
Rizzo, Giorgia ;
Orlandi, Stefano ;
Sadeghpour, Bahman ;
Wang, Xiaoxin X. ;
Jiang, Tao ;
Levi, Moshe ;
Pruzanski, Mark ;
Adorini, Luciano .
MOLECULAR PHARMACOLOGY, 2010, 78 (04) :617-630