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FXR signaling in the enterohepatic system.
Mol Cell Endocrinol. 2013 Apr 10; 368(1-2):17-29.MC

Abstract

Enterohepatic circulation serves to capture bile acids and other steroid metabolites produced in the liver and secreted to the intestine, for reabsorption back into the circulation and reuptake to the liver. This process is under tight regulation by nuclear receptor signaling. Bile acids, produced from cholesterol, can alter gene expression in the liver and small intestine via activating the nuclear receptors farnesoid X receptor (FXR; NR1H4), pregnane X receptor (PXR; NR1I2), vitamin D receptor (VDR; NR1I1), G protein coupled receptor TGR5, and other cell signaling pathways (JNK1/2, AKT and ERK1/2). Among these controls, FXR is known to be a major bile acid-responsive ligand-activated transcription factor and a crucial control element for maintaining bile acid homeostasis. FXR has a high affinity for several major endogenous bile acids, notably cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid. By responding to excess bile acids, FXR is a bridge between the liver and small intestine to control bile acid levels and regulate bile acid synthesis and enterohepatic flow. FXR is highly expressed in the liver and gut, relative to other tissues, and contributes to the maintenance of cholesterol/bile acid homeostasis by regulating a variety of metabolic enzymes and transporters. FXR activation also affects lipid and glucose metabolism, and can influence drug metabolism.

Authors+Show Affiliations

Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, United States.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

22609541

Citation

Matsubara, Tsutomu, et al. "FXR Signaling in the Enterohepatic System." Molecular and Cellular Endocrinology, vol. 368, no. 1-2, 2013, pp. 17-29.
Matsubara T, Li F, Gonzalez FJ. FXR signaling in the enterohepatic system. Mol Cell Endocrinol. 2013;368(1-2):17-29.
Matsubara, T., Li, F., & Gonzalez, F. J. (2013). FXR signaling in the enterohepatic system. Molecular and Cellular Endocrinology, 368(1-2), 17-29. https://doi.org/10.1016/j.mce.2012.05.004
Matsubara T, Li F, Gonzalez FJ. FXR Signaling in the Enterohepatic System. Mol Cell Endocrinol. 2013 Apr 10;368(1-2):17-29. PubMed PMID: 22609541.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - FXR signaling in the enterohepatic system. AU - Matsubara,Tsutomu, AU - Li,Fei, AU - Gonzalez,Frank J, Y1 - 2012/05/17/ PY - 2012/01/11/received PY - 2012/04/18/revised PY - 2012/05/08/accepted PY - 2012/5/22/entrez PY - 2012/5/23/pubmed PY - 2013/9/11/medline SP - 17 EP - 29 JF - Molecular and cellular endocrinology JO - Mol. Cell. Endocrinol. VL - 368 IS - 1-2 N2 - Enterohepatic circulation serves to capture bile acids and other steroid metabolites produced in the liver and secreted to the intestine, for reabsorption back into the circulation and reuptake to the liver. This process is under tight regulation by nuclear receptor signaling. Bile acids, produced from cholesterol, can alter gene expression in the liver and small intestine via activating the nuclear receptors farnesoid X receptor (FXR; NR1H4), pregnane X receptor (PXR; NR1I2), vitamin D receptor (VDR; NR1I1), G protein coupled receptor TGR5, and other cell signaling pathways (JNK1/2, AKT and ERK1/2). Among these controls, FXR is known to be a major bile acid-responsive ligand-activated transcription factor and a crucial control element for maintaining bile acid homeostasis. FXR has a high affinity for several major endogenous bile acids, notably cholic acid, deoxycholic acid, chenodeoxycholic acid, and lithocholic acid. By responding to excess bile acids, FXR is a bridge between the liver and small intestine to control bile acid levels and regulate bile acid synthesis and enterohepatic flow. FXR is highly expressed in the liver and gut, relative to other tissues, and contributes to the maintenance of cholesterol/bile acid homeostasis by regulating a variety of metabolic enzymes and transporters. FXR activation also affects lipid and glucose metabolism, and can influence drug metabolism. SN - 1872-8057 UR - https://www.unboundmedicine.com/medline/citation/22609541/FXR_signaling_in_the_enterohepatic_system_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0303-7207(12)00270-5 DB - PRIME DP - Unbound Medicine ER -