Laboraroty Animal Research

Korean Association for Laboratory Animal Science (한국실험동물학회)
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Crosstalk between FXR and TGR5 controls glucagon-like peptide 1 secretion to maintain glycemic homeostasis

  • Kim, Hyeonhui (Severance Biomedical Science Institute, BK21 PLUS project for Medical Science, Gangnam Severance Hospital, Yonsei University College of Medicine) ;
  • Fang, Sungsoon (Severance Biomedical Science Institute, BK21 PLUS project for Medical Science, Gangnam Severance Hospital, Yonsei University College of Medicine)
  • Received : 2018.11.04
  • Accepted : 2018.12.05
  • Published : 2018.12.31
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Abstract

Though bile acids have been well known as digestive juice, recent studies have demonstrated that bile acids bind to their endogenous receptors, including Farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1; TGR5) and serve as hormone to control various biological processes, including cholesterol/bile acid metabolism, glucose/lipid metabolism, immune responses, and energy metabolism. Deficiency of those bile acid receptors has been reported to induce diverse metabolic syndromes such as obesity, hyperlipidemia, hyperglycemia, and insulin resistance. As consistent, numerous studies have reported alteration of bile acid signaling pathways in type II diabetes patients. Interestingly, bile acids have shown to activate TGR5 in intestinal L cells and enhance secretion of glucagon-like peptide 1 (GLP-1) to potentiate insulin secretion in response to glucose. Moreover, FXR has been shown to crosstalk with TGR5 to control GLP-1 secretion. Altogether, bile acid receptors, FXR and TGR5 are potent therapeutic targets for the treatment of metabolic diseases, including type II diabetes.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea, Yonsei University College of Medicine

References

  1. Chiang JY. Bile acid regulation of gene expression: roles of nuclear hormone receptors. Endocr Rev 2002; 23(4): 443-463. https://doi.org/10.1210/er.2000-0035
  2. Li T, Chiang JY. Nuclear receptors in bile acid metabolism. Drug Metab Rev 2013; 45(1): 145-155. https://doi.org/10.3109/03602532.2012.740048
  3. Russell DW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 2003; 72: 137-174. https://doi.org/10.1146/annurev.biochem.72.121801.161712
  4. Lu TT, Makishima M, Repa JJ, Schoonjans K, Kerr TA, Auwerx J, Mangelsdorf DJ. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors. Mol Cell 2000; 6(3): 507-515. https://doi.org/10.1016/S1097-2765(00)00050-2
  5. Makishima M, Okamoto AY, Repa JJ, Tu H, Learned RM, Luk A, Hull MV, Lustig KD, Mangelsdorf DJ, Shan B. Identification of a nuclear receptor for bile acids. Science 1999; 284(5418): 1362-1365. https://doi.org/10.1126/science.284.5418.1362
  6. Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature 2006; 439(7075): 484-489. https://doi.org/10.1038/nature04330
  7. Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, Macchiarulo A, Yamamoto H, Mataki C, Pruzanski M, Pellicciari R, Auwerx J, Schoonjans K. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab 2009; 10(3): 167-177. https://doi.org/10.1016/j.cmet.2009.08.001
  8. Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun 2005; 329(1): 386-390. https://doi.org/10.1016/j.bbrc.2005.01.139
  9. Pathak P, Liu H, Boehme S, Xie C, Krausz KW, Gonzalez F, Chiang JYL. Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism. J Biol Chem 2017; 292(26): 11055-11069. https://doi.org/10.1074/jbc.M117.784322
  10. Pathak P, Xie C, Nichols RG, Ferrell JM, Boehme S, Krausz KW, Patterson AD, Gonzalez FJ, Chiang JYL. Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism. Hepatology 2018; 68(4): 1574-1588. https://doi.org/10.1002/hep.29857
  11. Hong SH, Ahmadian M, Yu RT, Atkins AR, Downes M, Evans RM. Nuclear receptors and metabolism: from feast to famine. Diabetologia 2014; 57(5): 860-867. https://doi.org/10.1007/s00125-014-3209-9
  12. Yang X, Lamia KA, Evans RM. Nuclear receptors, metabolism, and the circadian clock. Cold Spring Harb Symp Quant Biol 2007; 72: 387-394. https://doi.org/10.1101/sqb.2007.72.058
  13. Ordentlich P, Downes M, Evans RM. Corepressors and nuclear hormone receptor function. Curr Top Microbiol Immunol 2001; 254: 101-116.
  14. McKenna NJ, Evans RM, O'Malley BW. Nuclear Receptor Signaling: a home for nuclear receptor and coregulator signaling research. Nucl Recept Signal 2014; 12: e006.
  15. Forman BM, Goode E, Chen J, Oro AE, Bradley DJ, Perlmann T, Noonan DJ, Burka LT, McMorris T, Lamph WW, Evans RM, Weinberger C. Identification of a nuclear receptor that is activated by farnesol metabolites. Cell 1995; 81(5): 687-693. https://doi.org/10.1016/0092-8674(95)90530-8
  16. Edwards PA, Kast HR, Anisfeld AM. BAREing it all: the adoption of LXR and FXR and their roles in lipid homeostasis. J Lipid Res 2002; 43(1): 2-12.
  17. Lee FY, Lee H, Hubbert ML, Edwards PA, Zhang Y. FXR, a multipurpose nuclear receptor. Trends Biochem Sci 2006; 31(10): 572-580. https://doi.org/10.1016/j.tibs.2006.08.002
  18. Fang S, Tsang S, Jones R, Ponugoti B, Yoon H, Wu SY, Chiang CM, Willson TM, Kemper JK. The p300 acetylase is critical for ligand-activated farnesoid X receptor (FXR) induction of SHP. J Biol Chem 2008; 283(50): 35086-35095. https://doi.org/10.1074/jbc.M803531200
  19. Zhang Y, Lee FY, Barrera G, Lee H, Vales C, Gonzalez FJ, Willson TM, Edwards PA. Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice. Proc Natl Acad Sci U S A 2006; 103(4): 1006-1011. https://doi.org/10.1073/pnas.0506982103
  20. Renga B, Mencarelli A, Vavassori P, Brancaleone V, Fiorucci S. The bile acid sensor FXR regulates insulin transcription and secretion. Biochim Biophys Acta 2010; 1802(3): 363-372. https://doi.org/10.1016/j.bbadis.2010.01.002
  21. Ma K, Saha PK, Chan L, Moore DD. Farnesoid X receptor is essential for normal glucose homeostasis. J Clin Invest 2006; 116(4): 1102-1109. https://doi.org/10.1172/JCI25604
  22. Duran-Sandoval D, Cariou B, Percevault F, Hennuyer N, Grefhorst A, van Dijk TH, Gonzalez FJ, Fruchart JC, Kuipers F, Staels B. The farnesoid X receptor modulates hepatic carbohydrate metabolism during the fasting-refeeding transition. J Biol Chem 2005; 280(33): 29971-29979. https://doi.org/10.1074/jbc.M501931200
  23. Jiang T, Wang XX, Scherzer P, Wilson P, Tallman J, Takahashi H, Li J, Iwahashi M, Sutherland E, Arend L, Levi M. Farnesoid X receptor modulates renal lipid metabolism, fibrosis, and diabetic nephropathy. Diabetes 2007; 56(10): 2485-2493. https://doi.org/10.2337/db06-1642
  24. Lambert G, Amar MJ, Guo G, Brewer HB Jr, Gonzalez FJ, Sinal CJ. The farnesoid X-receptor is an essential regulator of cholesterol homeostasis. J Biol Chem 2003; 278(4): 2563-2570. https://doi.org/10.1074/jbc.M209525200
  25. Claudel T, Staels B, Kuipers F. The Farnesoid X receptor: a molecular link between bile acid and lipid and glucose metabolism. Arterioscler Thromb Vasc Biol 2005; 25(10): 2020-2030. https://doi.org/10.1161/01.ATV.0000178994.21828.a7
  26. Cipriani S, Mencarelli A, Chini MG, Distrutti E, Renga B, Bifulco G, Baldelli F, Donini A, Fiorucci S. The bile acid receptor GPBAR-1 (TGR5) modulates integrity of intestinal barrier and immune response to experimental colitis. PLoS One 2011; 6(10): e25637. https://doi.org/10.1371/journal.pone.0025637
  27. Keitel V, Donner M, Winandy S, Kubitz R, Haussinger D. Expression and function of the bile acid receptor TGR5 in Kupffer cells. Biochem Biophys Res Commun 2008; 372(1): 78-84. https://doi.org/10.1016/j.bbrc.2008.04.171
  28. Lou G, Ma X, Fu X, Meng Z, Zhang W, Wang YD, Van Ness C, Yu D, Xu R, Huang W. GPBAR1/TGR5 mediates bile acidinduced cytokine expression in murine Kupffer cells. PLoS One 2014; 9(4): e93567. https://doi.org/10.1371/journal.pone.0093567
  29. Keitel V, Reinehr R, Gatsios P, Rupprecht C, Gorg B, Selbach O, Haussinger D, Kubitz R. The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells. Hepatology 2007; 45(3): 695-704. https://doi.org/10.1002/hep.21458
  30. Duboc H, Tache Y, Hofmann AF. The bile acid TGR5 membrane receptor: from basic research to clinical application. Dig Liver Dis 2014; 46(4): 302-312. https://doi.org/10.1016/j.dld.2013.10.021
  31. Li P, Zhu L, Yang X, Li W, Sun X, Yi B, Zhu S. Farnesoid X Receptor (FXR) Interacts with Camp Response Element Binding Protein (CREB) to Modulate Glucagon-Like Peptide-1 (7-36) Amide (GLP-1) Secretion by Intestinal L Cell. Cell Physiol Biochem 2018; 47(4): 1442-1452. https://doi.org/10.1159/000490836
  32. Velazquez-Villegas LA, Perino A, Lemos V, Zietak M, Nomura M, Pols TWH, Schoonjans K. TGR5 signalling promotes mitochondrial fission and beige remodelling of white adipose tissue. Nat Commun 2018; 9(1): 245. https://doi.org/10.1038/s41467-017-02068-0
  33. Trabelsi MS, Daoudi M, Prawitt J, Ducastel S, Touche V, Sayin SI, Perino A, Brighton CA4, Sebti Y, Kluza J, Briand O, Dehondt H, Vallez E, Dorchies E, Baud G, Spinelli V, Hennuyer N, Caron S, Bantubungi K, Caiazzo R, Reimann F, Marchetti P, Lefebvre P, Backhed F, Gribble FM, Schoonjans K, Pattou F, Tailleux A, Staels B, Lestavel S. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells. Nat Commun 2015; 6: 7629. https://doi.org/10.1038/ncomms8629
  34. Fang S, Suh JM, Reilly SM, Yu E, Osborn O, Lackey D, Yoshihara E, Perino A, Jacinto S, Lukasheva Y, Atkins AR, Khvat A, Schnabl B, Yu RT, Brenner DA, Coulter S, Liddle C, Schoonjans K, Olefsky JM, Saltiel AR, Downes M, Evans RM. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med 2015; 21(2): 159-165. https://doi.org/10.1038/nm.3760
  35. Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva-Datchary P, Myronovych A, Karns R, Wilson-Perez HE, Sandoval DA, Kohli R, Backhed F, Seeley RJ. FXR is a molecular target for the effects of vertical sleeve gastrectomy. Nature 2014; 509(7499): 183-188. https://doi.org/10.1038/nature13135
  36. Gerhard GS, Styer AM, Wood GC, Roesch SL, Petrick AT, Gabrielsen J, Strodel WE, Still CD, Argyropoulos G. A role for fibroblast growth factor 19 and bile acids in diabetes remission after Roux-en-Y gastric bypass. Diabetes Care 2013; 36(7): 1859-1864. https://doi.org/10.2337/dc12-2255
  37. Kohli R, Bradley D, Setchell KD, Eagon JC, Abumrad N, Klein S. Weight loss induced by Roux-en-Y gastric bypass but not laparoscopic adjustable gastric banding increases circulating bile acids. J Clin Endocrinol Metab 2013; 98(4): E708-712. https://doi.org/10.1210/jc.2012-3736
  38. Rabiee A, Magruder JT, Salas-Carrillo R, Carlson O, Egan JM, Askin FB, Elahi D, Andersen DK. Hyperinsulinemic hypoglycemia after Roux-en-Y gastric bypass: unraveling the role of gut hormonal and pancreatic endocrine dysfunction. J Surg Res 2011; 167(2): 199-205. https://doi.org/10.1016/j.jss.2010.09.047

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