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Review
. 2006 Apr 5;25(7):1419-25.
doi: 10.1038/sj.emboj.7601049. Epub 2006 Mar 16.

Endocrine functions of bile acids

Sander M Houten  1 , Mitsuhiro Watanabe, Johan Auwerx
Affiliations
Review

Endocrine functions of bile acids

Sander M Houten et al. EMBO J. .

Abstract

Bile acids (BAs), a group of structurally diverse molecules that are primarily synthesized in the liver from cholesterol, are the chief components of bile. Besides their well-established roles in dietary lipid absorption and cholesterol homeostasis, it has recently emerged that BAs are also signaling molecules, with systemic endocrine functions. BAs activate mitogen-activated protein kinase pathways, are ligands for the G-protein-coupled receptor TGR5, and activate nuclear hormone receptors such as farnesoid X receptor alpha. Through activation of these diverse signaling pathways, BAs can regulate their own enterohepatic circulation, but also triglyceride, cholesterol, energy, and glucose homeostasis. Thus, BA-controlled signaling pathways are promising novel drug targets to treat common metabolic diseases, such as obesity, type II diabetes, hyperlipidemia, and atherosclerosis.

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Figures

Figure 1
Figure 1
(A) Structure of selected BAs. (B) FXRα target genes involved in the enterohepatic recycling and detoxification of BAs. Genes whose expression is directly induced by BAs and FXRα are in yellow rectangles; those in pink rectangles are inhibited by BAs. BACS, BA-CoA synthetase; BAT, BA-CoA: amino acid N-acetyltransferase; BSEP, bile salt export pump; MDR3, multidrug resistance 3 p-glycoprotein; MRP2, multidrug resistance-associated protein 2; IBABP, ileal BA-binding protein; CYP8B1, sterol 12α-hydroxylase; NTCP, sodium taurocholate cotransporting polypeptide; ASBT, apical sodium-dependent bile salt transporter.
Figure 2
Figure 2
Respective situations that cause high (left panel) and low (right) transhepatic flux of BAs and their principle functional consequences.
Figure 3
Figure 3
Schematic representation of the control of BAs on BA, triglyceride and energy homeostasis. TR, thyroid hormone receptor.
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References

    1. Angelin B, Einarsson K, Hellstrom K, Leijd B (1978) Effects of cholestyramine and chenodeoxycholic acid on the metabolism of endogenous triglyceride in hyperlipoproteinemia. J Lipid Res 19: 1017–1024 - PubMed
    1. Brendel C, Schoonjans K, Botrugno OA, Treuter E, Auwerx J (2002) The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity. Mol Endocrinol 16: 2065–2076 - PubMed
    1. Chiang JY (2002) Bile acid regulation of gene expression: roles of nuclear hormone receptors. Endocr Rev 23: 443–463 - PubMed
    1. Claudel T, Staels B, Kuipers F (2005) The farnesoid X receptor. A molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol 25: 2020–2030 - PubMed
    1. Cohen DE (2003) Pathogenesis of gallstones. In Hepatology: A Textbook of Liver Disease, Zakim D, Boyer TD (eds) pp 1713–1743. Philadelphia: Saunders

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