The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation

Journal of Hepatology

Volumn 54, Issue 6, 2011, Pages 1263-1272

  Pols, Thijs W H ^a   Noriega, Lilia G ^a   Nomura, Mitsunori ^a   Auwerx, Johan ^a   Schoonjans, Kristina ^a  

^a EPFL   (Switzerland)

Author keywords

Bile acids; Diabetes; Energy homeostasis; FXR; G protein coupled receptor; GLP 1; Nuclear receptors; TGR5

Indexed keywords

6 ETHYL 23 METHYL CHOLIC ACID; AMIDE; BETULIC ACID; BILE ACID; CELL NUCLEUS RECEPTOR; CHENODEOXYCHOLIC ACID; CHOLIC ACID; FXR ALPHA RECEPTOR; GLUCOSE; INSULIN; MEMBRANE RECEPTOR; OLEANOLIC ACID; PHOSPHOTRANSFERASE; QUINONE DERIVATIVE; TGR5 PROTEIN; UNCLASSIFIED DRUG; URSODEOXYCHOLIC ACID;

ASTROCYTE; BILE ACID SYNTHESIS; BODY WEIGHT; BROWN ADIPOSE TISSUE; CELL TYPE; CIRCULATION; CONCENTRATION (PARAMETERS); DIABETES MELLITUS; ENDOTHELIUM CELL; ENERGY EXPENDITURE; ENTEROENDOCRINE CELL; ENZYME REGULATION; EPITHELIUM CELL; FOOD INTAKE; GALLBLADDER; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; HUMAN; IMMUNE RESPONSE; INFLAMMATION; INSULIN SENSITIVITY; LIPID ABSORPTION; LIPID METABOLISM; LIPID TRANSPORT; LIVER FUNCTION; MACROPHAGE; METABOLIC SYNDROME X; METABOLISM; MUSCLE CELL; NERVE CELL; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN TARGETING; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; SMOOTH MUSCLE FIBER;

ANIMALS; BILE ACIDS AND SALTS; GLUCOSE; HUMANS; IMMUNOLOGIC FACTORS; INFLAMMATION; INSULIN RESISTANCE; LIVER; METABOLIC SYNDROME X; MICE; MODELS, BIOLOGICAL; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION;

EID: 79956088562     PISSN: 01688278     EISSN: 01688278     Source Type: Journal    
DOI: 10.1016/j.jhep.2010.12.004     Document Type: Review

References (109)

1. D.W. Russell Fifty years of advances in bile acid synthesis and metabolism J Lipid Res 50 2009 S120 S125
2. D.W. Russell, and K.D. Setchell Bile acid biosynthesis Biochemistry 31 1992 4737 4749
3. T. Inagaki, A. Moschetta, Y.K. Lee, L. Peng, G. Zhao, and M. Downes Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor Proc Natl Acad Sci USA 103 2006 3920 3925 (Pubitemid 43376656)
4. S.M. Houten, M. Watanabe, and J. Auwerx Endocrine functions of bile acids EMBO J 25 2006 1419 1425
5. C. Thomas, R. Pellicciari, M. Pruzanski, J. Auwerx, and K. Schoonjans Targeting bile-acid signalling for metabolic diseases Nat Rev Drug Discov 7 2008 678 693
6. D.W. Russell The enzymes, regulation, and genetics of bile acid synthesis Annu Rev Biochem 72 2003 137 174 (Pubitemid 36930444)
7. S. Ishibashi, M. Schwarz, P.K. Frykman, J. Herz, and D.W. Russell Disruption of cholesterol 7alpha-hydroxylase gene in mice. I. Postnatal lethality reversed by bile acid and vitamin supplementation J Biol Chem 271 1996 18017 18023 (Pubitemid 26250787)
8. M. Schwarz, E.G. Lund, K.D. Setchell, H.J. Kayden, J.E. Zerwekh, and I. Bjorkhem Disruption of cholesterol 7alpha-hydroxylase gene in mice. II. Bile acid deficiency is overcome by induction of oxysterol 7alpha-hydroxylase J Biol Chem 271 1996 18024 18031 (Pubitemid 26250788)
9. J.B. Kwakye, S. Barnes, and R.B. Diasio Identification of bile acid coenzyme A synthetase in rat kidney J Lipid Res 34 1993 95 99 (Pubitemid 23016625)
10. C.N. Falany, M.R. Johnson, S. Barnes, and R.B. Diasio Glycine and taurine conjugation of bile acids by a single enzyme. Molecular cloning and expression of human liver bile acid CoA: amino acid N-acyltransferase J Biol Chem 269 1994 19375 19379
11. B. Hubbard, H. Doege, S. Punreddy, H. Wu, X. Huang, and V.K. Kaushik Mice deleted for fatty acid transport protein 5 have defective bile acid conjugation and are protected from obesity Gastroenterology 130 2006 1259 1269
12. N.Y. Kalaany, and D.J. Mangelsdorf LXRS and FXR: the yin and yang of cholesterol and fat metabolism Annu Rev Physiol 68 2006 159 191
13. S.J. Bensinger, and P. Tontonoz Integration of metabolism and inflammation by lipid-activated nuclear receptors Nature 454 7203 2008 470 477
14. W. Chen, G. Chen, D.L. Head, D.J. Mangelsdorf, and D.W. Russell Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of mice Cell Metab 5 2007 73 79 (Pubitemid 44933109)
15. D.J. Peet, S.D. Turley, W. Ma, B.A. Janowski, J.M. Lobaccaro, and R.E. Hammer Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha Cell 93 1998 693 704 (Pubitemid 28257577)
16. B. Goodwin, S.A. Jones, R.R. Price, M.A. Watson, D.D. McKee, and L.B. Moore SHP-1, and LRH-1 represses bile acid biosynthesis Mol Cell 6 2000 517 526
17. T.T. Lu, M. Makishima, J.J. Repa, K. Schoonjans, T.A. Kerr, and J. Auwerx Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors Mol Cell 6 2000 507 515
18. C. Brendel, K. Schoonjans, O.A. Botrugno, E. Treuter, and J. Auwerx The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity Mol Endocrinol 16 2002 2065 2076 (Pubitemid 35013455)
19. D. Stroup, M. Crestani, and J.Y. Chiang Identification of a bile acid response element in the cholesterol 7 alpha-hydroxylase gene CYP7A Am J Physiol 273 1997 G508 G517
20. E. De Fabiani, N. Mitro, A.C. Anzulovich, A. Pinelli, G. Galli, and M. Crestani The negative effects of bile acids and tumor necrosis factor-alpha on the transcription of cholesterol 7alpha-hydroxylase gene (CYP7A1) converge to hepatic nuclear factor-4: a novel mechanism of feedback regulation of bile acid synthesis mediated by nuclear receptors J Biol Chem 276 2001 30708 30716
21. M. Zhang, and J.Y. Chiang Transcriptional regulation of the human sterol 12alpha-hydroxylase gene (CYP8B1): roles of heaptocyte nuclear factor 4alpha in mediating bile acid repression J Biol Chem 276 2001 41690 41699
22. A. del Castillo-Olivares, and G. Gil Alpha 1-fetoprotein transcription factor is required for the expression of sterol 12alpha-hydroxylase, the specific enzyme for cholic acid synthesis. Potential role in the bile acid-mediated regulation of gene transcription J Biol Chem 275 2000 17793 17799 (Pubitemid 30430830)
23. C. Mataki, B.C. Magnier, S.M. Houten, J.S. Annicotte, C. Argmann, and C. Thomas Compromised intestinal lipid absorption in mice with a liver-specific deficiency of liver receptor homolog 1 Mol Cell Biol 27 2007 8330 8339 (Pubitemid 350234244)
24. Y.K. Lee, D.R. Schmidt, C.L. Cummins, M. Choi, L. Peng, and Y. Zhang Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for feedback regulation of bile acid synthesis Mol Endocrinol 22 2008 1345 1356 (Pubitemid 351786995)
25. T. Inagaki, M. Choi, A. Moschetta, L. Peng, C.L. Cummins, and J.G. McDonald Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis Cell Metab 2 2005 217 225
26. B.C. Lin, M. Wang, C. Blackmore, and L.R. Desnoyers Liver-specific activities of FGF19 require Klotho beta J Biol Chem 282 2007 27277 27284 (Pubitemid 47501977)
27. M. Choi, A. Moschetta, A.L. Bookout, L. Peng, M. Umetani, and S.R. Holmstrom Identification of a hormonal basis for gallbladder filling Nat Med 12 2006 1253 1255 (Pubitemid 44706926)
28. S.M. Houten, and J. Auwerx The enterohepatic nuclear receptors are major regulators of the enterohepatic circulation of bile salts Ann Med 36 2004 482 491 (Pubitemid 39490958)
29. E.R. Schiff, N.C. Small, and J.M. Dietschy Characterization of the kinetics of the passive and active transport mechanisms for bile acid absorption in the small intestine and colon of the rat J Clin Invest 51 1972 1351 1362
30. P. Oelkers, L.C. Kirby, J.E. Heubi, and P.A. Dawson Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2) J Clin Invest 99 1997 1880 1887 (Pubitemid 27175935)
31. S.M. Houten, D.H. Volle, C.L. Cummins, D.J. Mangelsdorf, and J. Auwerx In vivo imaging of farnesoid X receptor activity reveals the ileum as the primary bile acid signaling tissue Mol Endocrinol 21 2007 1312 1323 (Pubitemid 46984739)
32. G.A. Kullak-Ublick, B. Stieger, and P.J. Meier Enterohepatic bile salt transporters in normal physiology and liver disease Gastroenterology 126 2004 322 342 (Pubitemid 38040747)
33. M. Wagner, G. Zollner, and M. Trauner New molecular insights into the mechanisms of cholestasis J Hepatol 51 2009 565 580
34. W. Seol, H.S. Choi, and D.D. Moore Isolation of proteins that interact specifically with the retinoid X receptor: two novel orphan receptors Mol Endocrinol 9 1995 72 85
35. B.M. Forman, E. Goode, J. Chen, A.E. Oro, D.J. Bradley, and T. Perlmann Identification of a nuclear receptor that is activated by farnesol metabolites Cell 81 1995 687 693
36. M. Makishima, A.Y. Okamoto, J.J. Repa, H. Tu, R.M. Learned, and A. Luk Identification of a nuclear receptor for bile acids Science 284 5418 1999 1362 1365 (Pubitemid 29289663)
37. D.J. Parks, S.G. Blanchard, R.K. Bledsoe, G. Chandra, T.G. Consler, and S.A. Kliewer Bile acids: natural ligands for an orphan nuclear receptor Science 284 5418 1999 1365 1368 (Pubitemid 29289664)
38. H. Wang, J. Chen, K. Hollister, L.C. Sowers, and B.M. Forman Endogenous bile acids are ligands for the nuclear receptor FXR/BAR Mol Cell 3 1999 543 553 (Pubitemid 29268438)
39. K. Otte, H. Kranz, I. Kober, P. Thompson, M. Hoefer, and B. Haubold Identification of farnesoid X receptor beta as a novel mammalian nuclear receptor sensing lanosterol Mol Cell Biol 23 2003 864 872 (Pubitemid 36133505)
40. W. Xie, A. Radominska-Pandya, Y. Shi, C.M. Simon, M.C. Nelson, and E.S. Ong An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids Proc Natl Acad Sci USA 98 2001 3375 3380 (Pubitemid 32220853)
41. J.L. Staudinger, B. Goodwin, S.A. Jones, D. Hawkins-Brown, K.I. MacKenzie, and A. LaTour The nuclear receptor PXR is a lithocholic acid sensor that protects against liver toxicity Proc Natl Acad Sci USA 98 2001 3369 3374 (Pubitemid 32220852)
42. M. Makishima, T.T. Lu, W. Xie, G.K. Whitfield, H. Domoto, and R.M. Evans Vitamin D receptor as an intestinal bile acid sensor Science 296 5571 2002 1313 1316 (Pubitemid 34522785)
43. B. Goodwin, K.C. Gauthier, M. Umetani, M.A. Watson, M.I. Lochansky, and J.L. Collins Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor Proc Natl Acad Sci USA 100 2003 223 228 (Pubitemid 36078056)
44. M. Gascon-Barre, C. Demers, A. Mirshahi, S. Neron, S. Zalzal, and A. Nanci The normal liver harbors the vitamin D nuclear receptor in nonparenchymal and biliary epithelial cells Hepatology 37 2003 1034 1042 (Pubitemid 36538680)
45. D.R. Schmidt, S.R. Holmstrom, K. Fon Tacer, A.L. Bookout, S.A. Kliewer, and D.J. Mangelsdorf Regulation of bile acid synthesis by fat-soluble vitamins A and D J Biol Chem 2010
46. T. Li, and J.Y. Chiang Mechanism of rifampicin and pregnane X receptor inhibition of human cholesterol 7 alpha-hydroxylase gene transcription Am J Physiol Gastrointest Liver Physiol 288 2005 G74 G84
47. S. Gupta, R.T. Stravitz, P. Dent, and P.B. Hylemon Down-regulation of cholesterol 7alpha-hydroxylase (CYP7A1) gene expression by bile acids in primary rat hepatocytes is mediated by the c-Jun N-terminal kinase pathway J Biol Chem 276 2001 15816 15822
48. J.A. Holt, G. Luo, A.N. Billin, J. Bisi, Y.Y. McNeill, and K.F. Kozarsky Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis Genes Dev 17 2003 1581 1591 (Pubitemid 36828786)
49. D. Qiao, E.D. Stratagouleas, and J.D. Martinez Activation and role of mitogen-activated protein kinases in deoxycholic acid-induced apoptosis Carcinogenesis 22 2001 35 41 (Pubitemid 32098141)
50. P. Dent, Y. Fang, S. Gupta, E. Studer, C. Mitchell, and S. Spiegel Conjugated bile acids promote ERK1/2 and AKT activation via a pertussis toxin-sensitive mechanism in murine and human hepatocytes Hepatology 42 2005 1291 1299 (Pubitemid 43260031)
51. L. Qiao, S.I. Han, Y. Fang, J.S. Park, S. Gupta, and D. Gilfor Bile acid regulation of C/EBPbeta, CREB, and c-Jun function, via the extracellular signal-regulated kinase and c-Jun NH2-terminal kinase pathways, modulates the apoptotic response of hepatocytes Mol Cell Biol 23 2003 3052 3066 (Pubitemid 36459221)
52. A.A. Goldberg, V.R. Richard, P. Kyryakov, S.D. Bourque, A. Beach, and M.T. Burstein Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes Aging (Albany NY) 2 2010 393 414
53. K.L. Pierce, R.T. Premont, and R.J. Lefkowitz Seven-transmembrane receptors Nat Rev Mol Cell Biol 3 2002 639 650 (Pubitemid 34987785)
54. J.P. Raufman, P. Zimniak, and A. Bartoszko-Malik Lithocholyltaurine interacts with cholinergic receptors on dispersed chief cells from guinea pig stomach Am J Physiol 274 1998 G997 G1004
55. J.P. Raufman, Y. Chen, P. Zimniak, and K. Cheng Deoxycholic acid conjugates are muscarinic cholinergic receptor antagonists Pharmacology 65 2002 215 221 (Pubitemid 34765284)
56. Y. Le, P.M. Murphy, and J.M. Wang Formyl-peptide receptors revisited Trends Immunol 23 2002 541 548 (Pubitemid 35223553)
57. C. Ferrari, A. Macchiarulo, G. Costantino, and R. Pellicciari Pharmacophore model for bile acids recognition by the FPR receptor J Comput Aided Mol Des 20 2006 295 303
58. X. Chen, D. Yang, W. Shen, H.F. Dong, J.M. Wang, and J.J. Oppenheim Characterization of chenodeoxycholic acid as an endogenous antagonist of the G-coupled formyl peptide receptors Inflamm Res 49 2000 744 755 (Pubitemid 32097093)
59. J. Wess, R.M. Eglen, and D. Gautam Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development Nat Rev Drug Discov 6 2007 721 733 (Pubitemid 47342315)
60. D. Gautam, S.J. Han, F.F. Hamdan, J. Jeon, B. Li, and J.H. Li A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo Cell Metab 3 2006 449 461 (Pubitemid 43811775)
61. T. Maruyama, Y. Miyamoto, T. Nakamura, Y. Tamai, H. Okada, and E. Sugiyama Identification of membrane-type receptor for bile acids (M-BAR) Biochem Biophys Res Commun 298 2002 714 719 (Pubitemid 35356798)
62. Y. Kawamata, R. Fujii, M. Hosoya, M. Harada, H. Yoshida, and M. Miwa A G protein-coupled receptor responsive to bile acids J Biol Chem 278 2003 9435 9440 (Pubitemid 36800434)
63. M.R. Herbert, D.L. Siegel, L. Staszewski, C. Cayanan, U. Banerjee, and S. Dhamija Synthesis and SAR of 2-aryl-3-aminomethylquinolines as agonists of the bile acid receptor TGR5 Bioorg Med Chem Lett 20 2010 5718 5721
64. G. Vassileva, A. Golovko, L. Markowitz, S.J. Abbondanzo, M. Zeng, and S. Yang Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation Biochem J 398 2006 423 430 (Pubitemid 44453386)
65. V. Keitel, K. Cupisti, C. Ullmer, W.T. Knoefel, R. Kubitz, and D. Haussinger The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders Hepatology 50 2009 861 870
66. T. Maruyama, K. Tanaka, J. Suzuki, H. Miyoshi, N. Harada, and T. Nakamura Targeted disruption of G protein-coupled bile acid receptor 1 (Gpbar1/M-Bar) in mice J Endocrinol 191 2006 197 205 (Pubitemid 44756522)
67. V. Keitel, R. Reinehr, P. Gatsios, C. Rupprecht, B. Gorg, and O. Selbach The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells Hepatology 45 2007 695 704 (Pubitemid 46450621)
68. V. Keitel, M. Donner, S. Winandy, R. Kubitz, and D. Haussinger Expression and function of the bile acid receptor TGR5 in Kupffer cells Biochem Biophys Res Commun 372 2008 78 84 (Pubitemid 351778164)
69. M. Watanabe, S.M. Houten, C. Mataki, M.A. Christoffolete, B.W. Kim, and H. Sato Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation Nature 439 7075 2006 484 489 (Pubitemid 43152840)
70. D.P. Poole, C. Godfrey, F. Cattaruzza, G.S. Cottrell, J.G. Kirkland, and J.C. Pelayo Expression and function of the bile acid receptor GpBAR1 (TGR5) in the murine enteric nervous system Neurogastroenterol Motil 2010
71. C. Thomas, A. Gioiello, L. Noriega, A. Strehle, J. Oury, and G. Rizzo TGR5-mediated bile acid sensing controls glucose homeostasis Cell Metab 10 2009 167 177
72. G. Vassileva, W. Hu, L. Hoos, G. Tetzloff, S. Yang, and L. Liu Gender-dependent effect of Gpbar1 genetic deletion on the metabolic profiles of diet-induced obese mice J Endocrinol 2010
73. B. Lavoie, O.B. Balemba, C. Godfrey, C.A. Watson, G. Vassileva, and C.U. Corvera Hydrophobic bile salts inhibit gallbladder smooth muscle function via stimulation of GPBAR1 receptors and activation of KATP channels J Physiol 2010
74. V. Keitel, C. Ullmer, and D. Haussinger The membrane-bound bile acid receptor TGR5 (Gpbar-1) is localized in the primary cilium of cholangiocytes Biol Chem 391 2010 785 789
75. G. Brufau, M.J. Bahr, B. Staels, T. Claudel, J. Ockenga, and K.H. Boker Plasma bile acids are not associated with energy metabolism in humans Nutr Metab (Lond) 7 2010 73
76. O. Shaham, R. Wei, T.J. Wang, C. Ricciardi, G.D. Lewis, and R.S. Vasan Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity Mol Syst Biol 4 2008 214
77. M.E. Patti, S.M. Houten, A.C. Bianco, R. Bernier, P.R. Larsen, and J.J. Holst Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism Obesity (Silver Spring) 17 2009 1671 1677
78. C. Thomas, J. Auwerx, and K. Schoonjans Bile acids and the membrane bile acid receptor TGR5-connecting nutrition and metabolism Thyroid 18 2008 167 174 (Pubitemid 351271532)
79. S. Katsuma, A. Hirasawa, and G. Tsujimoto Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1 Biochem Biophys Res Commun 329 2005 386 390 (Pubitemid 40255465)
80. T. Tolessa, M. Gutniak, J.J. Holst, S. Efendic, and P.M. Hellstrom Inhibitory effect of glucagon-like peptide-1 on small bowel motility. Fasting but not fed motility inhibited via nitric oxide independently of insulin and somatostatin J Clin Invest 102 1998 764 774 (Pubitemid 28399609)
81. H. Sato, C. Genet, A. Strehle, C. Thomas, A. Lobstein, and A. Wagner Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea Biochem Biophys Res Commun 362 2007 793 798 (Pubitemid 47398870)
82. J.M. Olefsky, and C.K. Glass Macrophages, inflammation, and insulin resistance Annu Rev Physiol 72 2010 219 246
83. T. Yoshimura, C. Kurita, T. Nagao, E. Usami, T. Nakao, and S. Watanabe Inhibition of tumor necrosis factor-alpha and interleukin-1-beta production by beta-adrenoceptor agonists from lipopolysaccharide-stimulated human peripheral blood mononuclear cells Pharmacology 54 1997 144 152 (Pubitemid 27136077)
84. C.E. Scott-Conner, and J.B. Grogan The pathophysiology of biliary obstruction and its effect on phagocytic and immune function J Surg Res 57 1994 316 336 (Pubitemid 24262407)
85. J.R. Hov, V. Keitel, J.K. Laerdahl, L. Spomer, E. Ellinghaus, and A. ElSharawy Mutational characterization of the bile acid receptor TGR5 in primary sclerosing cholangitis PLoS One 5 2010 e12403
86. G. Baffy Kupffer cells in non-alcoholic fatty liver disease: the emerging view J Hepatol 51 2009 212 223
87. S.M. Grundy, E.H. Ahrens Jr., and G. Salen Interruption of the enterohepatic circulation of bile acids in man: comparative effects of cholestyramine and ileal exclusion on cholesterol metabolism J Lab Clin Med 78 1971 94 121
88. P.J. Nestel, and A. Poyser Changes in cholesterol synthesis and excretion when cholesterol intake is increased Metabolism 25 1976 1591 1599 (Pubitemid 8002404)
89. B. Angelin, K. Einarsson, and K. Hellstrom Effect of cholestyramine on bile acid kinetics in patients with portal cirrhosis of the liver. Evidence of a selective defect in the formation of cholic acid Am J Dig Dis 23 1978 1115 1120 (Pubitemid 9126611)
90. C. Glicksman, D.J. Pournaras, M. Wright, R. Roberts, D. Mahon, and R. Welbourn Postprandial plasma bile acid responses in normal weight and obese subjects Ann Clin Biochem 2010
91. M. Kobayashi, H. Ikegami, T. Fujisawa, K. Nojima, Y. Kawabata, and S. Noso Prevention and treatment of obesity, insulin resistance, and diabetes by bile acid-binding resin Diabetes 56 2007 239 247
92. T. Yamakawa, T. Takano, H. Utsunomiya, K. Kadonosono, and A. Okamura Effect of colestimide therapy for glycemic control in type 2 diabetes mellitus with hypercholesterolemia Endocr J 54 2007 53 58 (Pubitemid 46481671)
93. V.A. Fonseca, J. Rosenstock, A.C. Wang, K.E. Truitt, and M.R. Jones Colesevelam HCl improves glycemic control and reduces LDL cholesterol in patients with inadequately controlled type 2 diabetes on sulfonylurea-based therapy Diabetes Care 31 2008 1479 1484
94. K. Mussig, H. Staiger, F. Machicao, J. Machann, F. Schick, and S.A. Schafer Preliminary report: genetic variation within the GPBAR1 gene is not associated with metabolic traits in white subjects at an increased risk for type 2 diabetes mellitus Metabolism 58 2009 1809 1811
95. R. Pellicciari, H. Sato, A. Gioiello, G. Costantino, A. Macchiarulo, and B.M. Sadeghpour Nongenomic actions of bile acids. Synthesis and preliminary characterization of 23- and 6,23-alkyl-substituted bile acid derivatives as selective modulators for the G-protein coupled receptor TGR5 J Med Chem 50 2007 4265 4268 (Pubitemid 47378826)
96. A. Macchiarulo, A. Gioiello, C. Thomas, A. Massarotti, R. Nuti, and E. Rosatelli Molecular field analysis and 3D-quantitative structure-activity relationship study (MFA 3D-QSAR) unveil novel features of bile acid recognition at TGR5 J Chem Inf Model 48 2008 1792 1801
97. R. Pellicciari, A. Gioiello, A. Macchiarulo, C. Thomas, E. Rosatelli, and B. Natalini Discovery of 6alpha-ethyl-23(S)-methylcholic acid (S-EMCA, INT-777) as a potent and selective agonist for the TGR5 receptor, a novel target for diabesity J Med Chem 52 2009 7958 7961
98. H. Sato, A. Macchiarulo, C. Thomas, A. Gioiello, M. Une, and A.F. Hofmann Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies J Med Chem 51 2008 1831 1841 (Pubitemid 351438866)
99. C. Genet, A. Strehle, C. Schmidt, G. Boudjelal, A. Lobstein, and K. Schoonjans Structure-activity relationship study of betulinic acid, a novel and selective TGR5 agonist, and its synthetic derivatives: potential impact in diabetes J Med Chem 53 2010 178 190
100. C. Genet, C. Schmidt, A. Strehle, K. Schoonjans, J. Auwerx, and R. Saladin Redefining the TGR5 triterpenoid binding pocket at the C-3 position ChemMedChem 5 2010 1983 1988
101. V. Keitel, B. Gorg, H.J. Bidmon, I. Zemtsova, L. Spomer, and K. Zilles The bile acid receptor TGR5 (Gpbar-1) acts as a neurosteroid receptor in brain Glia 58 2010 1794 1805
102. K.A. Evans, B.W. Budzik, S.A. Ross, D.D. Wisnoski, J. Jin, and R.A. Rivero Discovery of 3-aryl-4-isoxazolecarboxamides as TGR5 receptor agonists J Med Chem 52 2009 7962 7965
103. J.I. Yang, J.H. Yoon, S.J. Myung, G.Y. Gwak, W. Kim, and G.E. Chung Bile acid-induced TGR5-dependent c-Jun-N terminal kinase activation leads to enhanced caspase 8 activation in hepatocytes Biochem Biophys Res Commun 361 2007 156 161 (Pubitemid 47102281)
104. H. Yasuda, S. Hirata, K. Inoue, H. Mashima, H. Ohnishi, and M. Yoshiba Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells Biochem Biophys Res Commun 354 2007 154 159 (Pubitemid 46131451)
105. M.S. Desai, Z. Shabier, M. Taylor, F. Lam, S. Thevananther, and A. Kosters Hypertrophic cardiomyopathy and dysregulation of cardiac energetics in a mouse model of biliary fibrosis Hepatology 51 2010 2097 2107
106. G. Perides, J.M. Laukkarinen, G. Vassileva, and M.L. Steer Biliary acute pancreatitis in mice is mediated by the G-protein-coupled cell surface bile acid receptor Gpbar1 Gastroenterology 138 2010 715 725
107. D.L. Motola, C.L. Cummins, V. Rottiers, K.K. Sharma, T. Li, and Y. Li Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegans Cell 124 2006 1209 1223
108. B. Gerisch, V. Rottiers, D. Li, D.L. Motola, C.L. Cummins, and H. Lehrach A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling Proc Natl Acad Sci USA 104 2007 5014 5019 (Pubitemid 47186168)
109. R.H. Houtkooper, R.W. Williams, and J. Auwerx Metabolic networks of longevity Cell 142 2010 9 14