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Bile Acids and Their Receptors

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Signaling Pathways in Liver Diseases

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Abstract

In animals, cholesterol is an essential molecule for membrane formation and synthesis of hormones and bile acids (BAs). Excess of cholesterol, either due to food consumption or endogenous synthesis, leads to gallstone formation and atherosclerosis. BAs produced from cholesterol and free cholesterol are secreted into bile and subsequently eliminated via feces, the only route to eliminate excess of cholesterol. As a major secretory pathway, the different steps of bile formation are precisely controlled and coordinated mostly via a complex network of nuclear receptors. Nuclear receptors (NRs) are transcription factors that, upon ligand binding and cofactors recruitment, modulate polymerase II activity and therefore gene expression, after binding to highly specific DNA response elements located in gene promoters. The Farnesoid X Receptor (FXR, NR1H4) [1] is a bile acid activated nuclear receptor [2–4], regulating several key steps of hepatic physiology such as bile formation, phase I/II metabolism, and glucose, lipid, and lipoprotein metabolisms [5]. Moreover, other NRs like Pregnane X Receptor (PXR; NRI2) [6, 7], Vitamin D Receptor (VDR; NR1I1) [8], and Constitutive Androstane Receptor (CAR; NR1I3) [9, 10] were identified as additional bile acid responsive NRs. In addition to NRs, BAs can also activate a membrane receptor for BAs (TGR5/BG37) [11, 12], a step which does not require bile acid uptake into target cells. Both FXR and TGR5 may play an important role in the pathogenesis and treatment of a variety of hepatic and extrahepatic metabolic disorders including cholestasis, fatty liver, diabetes, dylipidemia, and atherosclerosis.

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  1. Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University, Graz, Stiftingalstrasse 24, 8010, Graz, Austria

    Thierry Claudel & Michael Trauner

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    Pierre-Alain Clavien

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Claudel, T., Trauner, M. (2010). Bile Acids and Their Receptors. In: Dufour, JF., Clavien, PA. (eds) Signaling Pathways in Liver Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-00150-5_21

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