TGR5 controls bile acid composition and gallbladder function to protect the liver from bile acid overload

Merlen, 2017, Bile acids and their receptors during liver regeneration: “Dangerous protectors”, Mol Aspects Med, 56, 25, 10.1016/j.mam.2017.03.002 Doignon, 2011, Immediate neuroendocrine signaling after partial hepatectomy through acute portal hyperpressure and cholestasis, J Hepatol, 54, 481, 10.1016/j.jhep.2010.07.012 Besnard, 2016, The P2X4 purinergic receptor impacts liver regeneration after partial hepatectomy in mice through the regulation of biliary homeostasis, Hepatology, 64, 941, 10.1002/hep.28675 Jourdainne, 2015, The bile acid receptor TGR5 and liver regeneration, Dig Dis, 33, 319, 10.1159/000371668 Pean, 2013, The receptor TGR5 protects the liver from bile acid overload during liver regeneration in mice, Hepatology, 58, 1451, 10.1002/hep.26463 Merlen, 2020, TGR5-dependent hepatoprotection through the regulation of biliary epithelium barrier function, Gut, 69, 146, 10.1136/gutjnl-2018-316975 Keitel, 2009, The membrane-bound bile acid receptor TGR5 is localized in the epithelium of human gallbladders, Hepatology, 50, 861, 10.1002/hep.23032 Reich, 2016, TGR5 is essential for bile acid-dependent cholangiocyte proliferation in vivo and in vitro, Gut, 65, 487, 10.1136/gutjnl-2015-309458 Lavoie, 2010, Hydrophobic bile salts inhibit gallbladder smooth muscle function via stimulation of GPBAR1 receptors and activation of KATP channels, J Physiol, 588, 3295, 10.1113/jphysiol.2010.192146 Li, 2011, The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling, Mol Endocrinol, 25, 1066, 10.1210/me.2010-0460 Vassileva, 2006, Targeted deletion of Gpbar1 protects mice from cholesterol gallstone formation, Biochem J, 398, 423, 10.1042/BJ20060537 Donepudi, 2017, G-protein-coupled bile acid receptor plays a key role in bile acid metabolism and fasting-induced hepatic steatosis in mice, Hepatology, 65, 813, 10.1002/hep.28707 Pathak, 2018, Intestine farnesoid X receptor agonist and the gut microbiota activate G-protein bile acid receptor-1 signaling to improve metabolism, Hepatology, 68, 1574, 10.1002/hep.29857 Ma, 2018, Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells, Science, 360, 10.1126/science.aan5931 Kong, 2019, FXR deficiency alters bile acid pool composition and exacerbates chronic alcohol induced liver injury, Dig Liver Dis, 51, 570, 10.1016/j.dld.2018.12.026 de Boer, 2020, A human-like bile acid pool induced by deletion of Cyp2c70 modulates effects of farnesoid X Receptor activation in mice, J Lipid Res, 61, 291, 10.1194/jlr.RA119000243 Thomas, 2009, TGR5-mediated bile acid sensing controls glucose homeostasis, Cell Metab, 10, 167, 10.1016/j.cmet.2009.08.001 Beuers, 2015, New paradigms in the treatment of hepatic cholestasis: from UDCA to FXR, PXR and beyond, J Hepatol, 62, S25, 10.1016/j.jhep.2015.02.023 Chiang, 2020, Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy, Am J Physiol Gastrointest Liver Physiol, 318, G554, 10.1152/ajpgi.00223.2019 McGavigan, 2017, TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice, Gut, 66, 226, 10.1136/gutjnl-2015-309871 Caruso, 2019, Dynamic and asymmetric changes of the microbial communities after cohousing in laboratory mice, Cell Rep, 27, 3401, 10.1016/j.celrep.2019.05.042 Debray, 2012, Defects in gallbladder emptying and bile acid homeostasis in mice with cystic fibrosis transmembrane conductance regulator deficiencies, Gastroenterology, 142, 1581, 10.1053/j.gastro.2012.02.033 Sato, 2007, Anti-hyperglycemic activity of a TGR5 agonist isolated from Olea europaea, Biochem Biophys Res Commun, 362, 793, 10.1016/j.bbrc.2007.06.130 Fuchs, 2017, Metabolic preconditioning protects BSEP/ABCB11-/- mice against cholestatic liver injury, J Hepatol, 66, 95, 10.1016/j.jhep.2016.08.017 Wang, 2019, Hydrophilic bile acids prevent liver damage caused by lack of biliary phospholipid in Mdr2-/- mice, J Lipid Res, 60, 85, 10.1194/jlr.M088070 Donkers, 2019, Developments in bile salt based therapies: a critical overview, Biochem Pharmacol, 161, 1, 10.1016/j.bcp.2018.12.018 Nevens, 2016, A placebo-controlled trial of obeticholic acid in primary biliary cholangitis, N Engl J Med, 375, 631, 10.1056/NEJMoa1509840 Kawamata, 2003, A G protein-coupled receptor responsive to bile acids, J Biol Chem, 278, 9435, 10.1074/jbc.M209706200 Carulli, 2000, Review article: effect of bile salt pool composition on hepatic and biliary functions, Aliment Pharmacol Ther, 14, 14, 10.1046/j.1365-2036.2000.014s2014.x Jahn, 2018, Bile acids in nonalcoholic steatohepatitis: pathophysiological driving force or innocent bystanders?, Hepatology, 67, 464, 10.1002/hep.29543 Hendrick, 2014, Bile acids stimulate chloride secretion through CFTR and calcium-activated Cl- channels in Calu-3 airway epithelial cells, Am J Physiol Lung Cel Mol Physiol, 307, L407, 10.1152/ajplung.00352.2013