Physiological effects of bile acids
Grinevich V.B., Sas E.I.
Military Medical Academy named after S.M.Kirov, St. Petersburg
Interest to studying the physiological properties of bile acids has increased after identification of the bile acids by the natural ligands of the farnesoid X receptor / nuclear bile acid receptor (FXR / BAR or NR1H4). Bile acids metabolism is closely connected with the cholesterol exchange. However, the study of effects on the farnesoid X receptor made it possible to establish mechanisms of the influence of bile acids not only on enterohepatic circulation and the functional activity of hepatocytes, but also on carbohydrate and lipid metabolism. The discovery of nuclear and membrane receptors of bile acids allowed a new assessment of the physiological feasibility of enterohepatic circulation as one of the mechanisms of metabolic regulation during meal or hunger. Mechanisms of pathogenetic influence on the hepatobiliary system are established in conditions of diabetes mellitus, obesity, dyslipidemia. Often this influence, as well as the actual effect on the synthesis of primary bile acids, is integrative, and sometimes also dual, which requires regular analysis of new data for the purpose of their subsequent integration into clinical practice.
Key words: bile acids, enterohepatic circulation, cholesterol, farnesoid X receptor.
For citation: Grinevich V.B., Sas E.I. Physiological effects of bile acids // RMJ. MEDICAL REVIEW. 2017. № 2. P. 87–91.
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37. Zollner G., Marschall H.U., Wagner M., Trauner M. Role of nuclear receptors in the adaptive response to bile acids and cholestasis: Pathogenetic and therapeutic considerations // Mol Pharm. 2006. Vol. 3. P. 231–251.
38. Guo G.L., Lambert G., Negishi M. et al. Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity // J Biol Chem. 2003. Vol. 278. P. 462–471.
2. Chiang J.Y.L. Regulation of bile acid synthesis // Front Biosci. 1998. Vol. 3. P. 176–193.
3. Duane W.C., Javitt N.B. 27-hydroxycholesterol. Production rates in normal human subjects // J Lipid Res. 2009. Vol. 40. P. 1194–1199.
4. Hofmann A.F. Detoxification of lithocholic acid, a toxic bile acid: Relevance to drug hepatotoxicity // Drug Metab Rev. 2004. Vol.36. P. 703–722.
5. Jansen P.L., Sturm E. Genetic cholestasis, causes and consequences for hepatobiliary transport // Liver Int. 2013. Vol. 23. P. 315–322.
6. Tabibian J.H., Masyuk A.I. et al. Physiology of Cholangiocytes // Compr Physiol. 2013. Vol. 3(1). P. 101–104.
7. Chiang J.Y.L. Bile Acid Metabolism and Signaling // Compr Physiol. 2013. Vol. 3. P. 1191–1212.
8. Kawamata Y., Fujii R., Hosoya M. et al. G protein-coupled receptor responsive to bile acids // J Biol Chem. 2003. Vol. 278. P. 435–440.
9. Amaral J.D., Viana R.J., Ramalho R.M. et al. Bile acids: Regulation of apoptosis by ursodeoxycholic acid // J Lipid Res. 2009. Vol. 50. P. 721–734.
10. Chiang J.Y. Bile acids: Regulation of synthesis // J Lipid Res. 2009. Vol. 50. P. 955–966.
11. Houten S.M., Watanabe M., Auwerx J. Endocrine functions of bile acids // Embo J. 2006. Vol. 25. P. 419–425.
12. Thomas C., Pellicciari R., Pruzanski M. et al. Targeting bile-acid signalling for metabolic diseases // Nat Rev Drug Discov. 2008. Vol. 7. P. 678–693.
13. Studer E., Zhou X., Zhao R. et. al. Conjugated bile acids activate the sphingosine-1-phosphate receptor 2 in primary rodent hepatocytes // Hepatology. 2012. Vol. 55. P. 267–276.
14. Myant N.B., Mitropoulos K.A. Cholesterol 7a-hydroxylase // J Lipid Res. 1999. Vol. 18. P. 135–153.
15. Li Y.C., Wang D.P., Chiang J.Y. Regulation of cholesterol 7 alpha-hydroxylase in the liver. Cloning, sequencing, and regulation of cholesterol 7 alpha-hydroxylase mRNA // J Biol Chem. 2012. Vol. 265. P. 212–219.
16. Pandak W.M., Stravitz R.T., Lucas V. et al. Hep G2 cells: A model for studies on regulation of human cholesterol 7alpha-hydroxylase at the molecular level // Am J Physiol. 2006. Vol. 270. P. 401–410.
17. Brown M.S., Goldstein J.L. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor // Cell. Vol. 2007. Vol. 89. P. 331–340.
18. Eloranta J.J., Kullak-Ublick G.A. The role of FXR in disorders of bile acid homeostasis // Physiology. 2008. Vol.23. P. 286–295.
19. Engelking L.J., Kuriyama H., Hammer R.E. et al. Overexpression of Insig-1 in the livers of transgenic mice inhibits SREBP processing and reduces insulin-stimulated lipogenesis // J Clin Invest. 2004. Vol. 113. P. 168–175.
20. Subbiah M.T.R., Yunker R.L. Cholesterol 7a-hydroxylase of rat liver: an insulin sensitive enzyme // Biochem Biophys Res Commun. 2004. Vol. 124. P. 896–902.
21. Shin D.J., Campos J.A., Gil G., Osborne T.F. PGC-1a activates CYP7A1 and bile acid biosynthesis // J Biol Chem. 2003. Vol. 278. Р. 50047–50052.
22. Li T., Kong X., Owsley E. et al. Insulin regulation of cholesterol 7{alpha}-hydroxylase expression in human hepatocytes: Roles of forkhead box o1 and sterol regulatory element-binding protein 1c // J Biol Chem. 2006. Vol. 281. P. 745–754.
23. Li T., Francl J.M., Boehme S. et el. Glucose and insulin induction of bile acid synthesis: Mechanisms and implication in diabetes and obesity // J Biol Chem. 2012. Vol. 287. P. 161–173.
24. Li T., Chanda D., Zhang Y. et al. Glucose stimulates cholesterol 7alpha-hydroxylase gene transcription in human hepatocytes // J Lipid Res. 2010. Vol. 51 P. 832–842.
25. Hylemon P.B., Zhou H., Pandak W.M. et al. Bile acids as regulatory molecules // J Lipid Res. 2009. Vol. 50. P. 509–520.
26. Fang Y., Studer E., Mitchell C. et al. Conjugated bile acids regulate hepatocyte glycogen synthase activity in vitro and in vivo via Galphai signaling // Mol Pharmacol. 2007. Vol. 71. P. 122–128.
27. Reinehr R., Becker S., Keitel V. et al. Bile salt-induced apoptosis involves NADPH oxidase isoform activation // Gastroenterology. 2005. Vol. 129. P. 209–231.
28. Patti M.E., Houten S.M., Bianco A.C. et al. Serum bile acids are higher in humans with prior gastric bypass: Potential contribution to improved glucose and lipid metabolism // Obesity. 2009. Vol.17. P. 671–677.
29. Watanabe M., Horai Y., Houten S.M. et al. Lowering bile acid pool size with a synthetic farnesoid X receptor (FXR) agonist induces obesity and diabetes through reduced energy expenditure // J Biol Chem. 2011. Vol. 26. P. 213–220.
30. Makishima M., Okamoto A.Y., Repa J.J. et al. Identification of a nuclear receptor for bile acids // Science. 1999. Vol. 24. P. 362–365.
31. Zhang Y., Edwards P.A. FXR signaling in metabolic disease // FEBS Lett. 2008. Vol. 582. P. 10–18.
32. Makishima M., Lu T.T., Xie W. et al. Vitamin D receptor as an intestinal bile acid sensor // Science. 2002. Vol. 296. P. 313–316.
33. Xie W., Radominska-Pandya A. et al. An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids // Proc Natl Acad Sci USA. 2001. Vol. 98. P. 375–380.
34. Tu H., Okamoto A.Y., Shan B. FXR, a bile acid receptor and biological sensor // Trends Cardiovasc Med. 2000. Vol. 10. P. 30–35.
35. Dawson P.A., Hubbert M., Haywood J. et al. The heteromeric organic solute transporter alpha-beta, Ostalpha-Ostbeta, is an ileal basolateral bile acid transporter // J Biol Chem. 2005. Vol. 280. P. 960–968.
36. Denson L.A., Sturm E., Echevarria W. et al. The orphan nuclear receptor, shp, mediates bile acid-induced inhibition of the rat bile acid transporter, ntcp // Gastroenterology. 2001. Vol. 121. P. 140–147.
37. Zollner G., Marschall H.U., Wagner M., Trauner M. Role of nuclear receptors in the adaptive response to bile acids and cholestasis: Pathogenetic and therapeutic considerations // Mol Pharm. 2006. Vol. 3. P. 231–251.
38. Guo G.L., Lambert G., Negishi M. et al. Complementary roles of farnesoid X receptor, pregnane X receptor, and constitutive androstane receptor in protection against bile acid toxicity // J Biol Chem. 2003. Vol. 278. P. 462–471.
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