Bile acids: regulation of synthesis

By J. Y. Chiang. Journal of Lipid Research, 2009

1,522 citations recorded by the source corpus.

Bile acids are physiological detergents that generate bile flow and facilitate intestinal absorption and transport of lipids, nutrients, and vitamins. Bile acids also are signaling molecules and inflammatory agents that rapidly activate nuclear receptors and cell signaling pathways that regulate lipid, glucose, and energy metabolism. The enterohepatic circulation of bile acids exerts important physiological functions not only in feedback inhibition of bile acid synthesis but also in control of whole-body lipid homeostasis. In the liver, bile acids activate a nuclear receptor, farnesoid X receptor (FXR), that induces an atypical nuclear receptor small heterodimer partner, which subsequently inhibits nuclear receptors, liver-related homolog-1, and hepatocyte nuclear factor 4&agr; and results in inhibiting transcription of the critical regulatory gene in bile acid synthesis, cholesterol 7&agr;-hydroxylase (CYP7A1). In the intestine, FXR induces an intestinal hormone, fibroblast growth factor 15 (FGF15; or FGF19 in human), which activates hepatic FGF receptor 4 (FGFR4) signaling to inhibit bile acid synthesis. However, the mechanism by which FXR/FGF19/FGFR4 signaling inhibits CYP7A1 remains unknown. Bile acids are able to induce FGF19 in human hepatocytes, and the FGF19 autocrine pathway may exist in the human livers. Bile acids and bile acid receptors are therapeutic targets for development of drugs for treatment of cholestatic liver diseases, fatty liver diseases, diabetes, obesity, and metabolic syndrome.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/58a9289cb52da57ba04da67c2751b2089d63d0c8

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In Molecular Biology

1. Tiangang Li
2. H. Ji
3. J. Y. Chiang
4. Jishu Zhou
5. G. Brent

In Oncology

1. Tiangang Li
2. J. Y. Chiang
3. P. Edwards
4. David S. Wishart

Citations in the corpus

• Effect of dietary bile acids on growth, body composition, lipid metabolism and microbiota in grass carp (Ctenopharyngodon idella) (2018, background): “FXR is activated by bile acids (Bilz et al., 2006); thus, in response to ligand binding, FXR plays a central role in the regulation of bile acid synthesis, excretion and transport, as well as lipid, glucose and energy metabolism (Chiang, 2009).”
• Thyroid hormone regulation of metabolism. (2014, background): “This cholesterol clearance pathway is regulated by a number of nuclear receptors that control the expression of cholesterol 7-hydroxylase (CYP7a1), the rate-limiting step in bile acid synthesis (41).”
• Bile Acid Signaling in Metabolic Disease and Drug Therapy (2014, background): “CDCA and UDCA have been used for gallstone dissolution and inborn errors of bile acid synthesis for many decades (Chiang, 2009).”
• Pleiotropic Roles of Bile Acids in Metabolism (2013, background): “…but not all, are actively transported into hepatocytes by sodium (Na+)-taurocholate cotransporting polypeptide (NTCP/SLC10A1) and organic anion transporters (OATPs; e.g., OAT1B2) that mediate the uptake of bile salts and bile acids, respectively (Figure 2A) (Chiang, 2009; Thomas et al., 2008).”
• Resveratrol Attenuates Trimethylamine-N-Oxide (TMAO)-Induced Atherosclerosis by Regulating TMAO Synthesis and Bile Acid Metabolism via Remodeling of the Gut Microbiota (2016, background): “In addition, the expression of CYP7A1 mRNA and protein, which is the rate-limiting enzyme in hepatic BA synthesis, was also investigated (29).”
• Bile Acid Metabolism and Signaling (2013, positive): “Many recent studies have provided strong evidence that bile acid-activate FXR plays a critical role in maintaining metabolic homeostasis (5, 33, 86, 87, 106, 189).”