TGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis
Open accessAbstract
TGR5 is a G protein-coupled receptor expressed in brown adipose tissue and muscle, where its activation by bile acids triggers an increase in energy expenditure and attenuates diet-induced obesity. Using a combination of pharmacological and genetic gain- and loss-of-function studies in vivo, we show here that TGR5 signaling induces intestinal glucagon-like peptide-1 (GLP-1) release, leading to improved liver and pancreatic function and enhanced glucose tolerance in obese mice. In addition, we show that the induction of GLP-1 release in enteroendocrine cells by 6alpha-ethyl-23(S)-methyl-cholic acid (EMCA, INT-777), a specific TGR5 agonist, is linked to an increase of the intracellular ATP/ADP ratio and a subsequent rise in intracellular calcium mobilization. Altogether, these data show that the TGR5 signaling pathway is critical in regulating intestinal GLP-1 secretion in vivo, and suggest that pharmacological targeting of TGR5 may constitute a promising incretin-based strategy for the treatment of diabesity and associated metabolic disorders.
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Bacteria-derived secondary bile acids (lithocholic acid, deoxycholic acid) can activate the G-protein coupled bile acid receptor TGR5 in L cells, promoting peripheral release of GLP-1 and PYY.
“Bacteria-derived secondary bile acids (lithocholic acid, deoxycholic acid) can activate the G-protein coupled bile acid receptor Gpbar1 receptor (TGR5) in L cells, promoting the peripheral release of GLP-1 and PYY (Katsuma et al., 2005;Thomas et al., 2009;Ullmer et al., 2013).”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Thomas et al., 2009
The Results section ('TGR5 overexpression modulates GLP-1 secretion in vivo'; page unavailable) reports that lithocholic acid induced GLP-1 release from ileal explants with high TGR5 expression. The Discussion also identifies TGR5-mediated GLP-1 release in enteroendocrine L cells. The copy does not establish the claim's bacterial origin, deoxycholic-acid example, or PYY release (searched: bacterial secondary bile acids, deoxycholic, and PYY). (LLM, conf=0.88)
Experimental — accuracy not yet measuredBile acids induce insulin secretion directly via the transmembrane bile acid receptor Takeda G protein-coupled receptor 5 on β cells and indirectly via stimulation of L-cell derived GLP-1 and subsequent insulin release.
“Bile acids induce insulin secretion directly via the transmembrane bile acid receptor Takeda G protein–coupled receptor 5 (on β cells and indirectly via stimulation of l-cell derived GLP-1 and subsequent insulin release (110–112).”
From Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease (2018) · cites this paper as [112]
TGR5 can theoretically protect against obesity and its complications via two distinct and potentially synergistic mechanisms: increased energy expenditure and improved insulin sensitivity.
“TGR5 is therefore a new and attractive target for treating obesity, since it can theoretically protect against obesity and its complications via two distinct and potentially synergistic mechanisms: increased energy expenditure and improved insulin sensitivity 148.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [148]
Bile acids increase energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin.
“Bile acids also increase energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin. This effect is dependent on induction of the type 2 iodothyronine deiodinase and is mediated by the binding of bile acids to a novel G-protein-coupled receptor TGR5 148.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [148]
The effect of bile acids on energy expenditure is dependent on induction of type 2 iodothyronine deiodinase and mediated by binding to TGR5.
“Bile acids also increase energy expenditure in brown adipose tissue, preventing obesity and resistance to insulin. This effect is dependent on induction of the type 2 iodothyronine deiodinase and is mediated by the binding of bile acids to a novel G-protein-coupled receptor TGR5 148.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [148]
One TGR5 agonist, INT-777, has shown efficacy in vivo, increasing energy expenditure and reducing adiposity in mice with diet-induced obesity.
“One promising TGR5 agonist, INT-777, has already shown efficacy in vivo, increasing energy expenditure and reducing adiposity in mice with diet-induced obesity 148,149.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [148]
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Cites
Abdominal obesity and metabolic syndrome
Després, J.-P., & Lemieux, I. (2006) · Nature · doi:10.1038/nature05488 · Cited by 4,354 · see citing works
Drucker, D. J., & Nauck, M. A. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69705-5 · Cited by 3,896 · see citing works
Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., Kodama, T., et al. (2006) · Nature · doi:10.1038/nature04330 · Cited by 2,220 · see citing works
Self-citationThe biology of incretin hormones
Drucker, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.004 · Cited by 2,210 · see citing works
A G Protein-coupled Receptor Responsive to Bile Acids
Kawamata, Y., Fujii, R., Hosoya, M., Harada, M., Yoshida, H., Miwa, M., Fukusumi, S., Habata, Y., Itoh, T., Shintani, Y., et al. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m209706200 · Cited by 1,628 · see citing works
Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120
Hirasawa, A., Tsumaya, K., Awaji, T., Katsuma, S., Adachi, T., Yamada, M., Sugimoto, Y., Miyazaki, S., & Tsujimoto, G. (2004) · Nature Medicine · doi:10.1038/nm1168 · Cited by 1,551 · see citing works
Targeting bile‐acid signalling for metabolic diseases
Thomas, C., Pellicciari, R., Pruzanski, M., Auwerx, J., & Schoonjans, K. (2008) · Nature Reviews Drug Discovery · doi:10.1038/nrd2619 · Cited by 1,422 · see citing works
Self-citationBile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c
渡辺, 光., Houten, S. M., Wang, L., Moschetta, A., Mangelsdorf, D. J., Heyman, R. A., Moore, D. D., & Auwerx, J. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci21025 · Cited by 1,398 · see citing works
Self-citationIdentification of membrane-type receptor for bile acids (M-BAR)
Maruyama, T., Miyamoto, Y., Nakamura, T., Tamai, Y., Okada, H., Sugiyama, E., Nakamura, T., Itadani, H., & Tanaka, K. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)02550-0 · Cited by 993 · see citing works
Activation of the nuclear receptor FXR improves hyperglycemia and hyperlipidemia in diabetic mice
Zhang, Y., Lee, F. Y., Barrera, G., Lee, H., Vales, C., Gonzalez, F. J., Willson, T. M., & Edwards, P. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506982103 · Cited by 961 · see citing works
Farnesoid X receptor is essential for normal glucose homeostasis
Ma, K. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25604 · Cited by 883 · see citing works
KATP channels as molecular sensors of cellular metabolism
Nichols, C. G. (2006) · Nature · doi:10.1038/nature04711 · Cited by 856 · see citing works
Katsuma, S., Hirasawa, A., & Tsujimoto, G. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.01.139 · Cited by 789 · see citing works
Glucose Sensing in L Cells: A Primary Cell Study
Reimann, F., Habib, A. M., Tolhurst, G., Parker, H. E., Rogers, G. J., & Gribble, F. M. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.11.002 · Cited by 733 · cited 9× · see citing works
“, 2006), and inspired by the fact that TGR5 is expressed in enteroendocrine cells (Katsuma et al., 2005; Reimann et al., 2008), we explored in this study whether TGR5 activation could alter glucose homeostasis.”
BackgroundResultInfluentialFeige, J. N., Lagouge, M., Canto, C., Strehle, A., Houten, S. M., Milne, J. C., Lambert, P. D., Mataki, C., Elliott, P. J., & Auwerx, J. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2008.08.017 · Cited by 719 · see citing works
Self-citationOverton, H. A., Babbs, A. J., Doel, S. M., Fyfe, M. C. T., Gardner, L. S., Griffin, G., Jackson, H. C., Procter, M. J., Rasamison, C. M., Tang‐Christensen, M., et al. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.02.004 · Cited by 656 · see citing works
Patti, M., Houten, S. M., Bianco, A. C., Bernier, R., Larsen, P. R., Holst, J. J., Badman, M. K., Maratos‐Flier, E., Mun, E. C., Pihlajamaki, J., et al. (2009) · Obesity · doi:10.1038/oby.2009.102 · Cited by 591 · see citing works
Self-citationEdfalk, S., Steneberg, P., & Edlund, H. (2008) · Diabetes · doi:10.2337/db08-0307 · Cited by 587 · see citing works
Endocrine functions of bile acids
Houten, S. M., 渡辺, 光., & Auwerx, J. H. (2006) · The EMBO Journal · doi:10.1038/sj.emboj.7601049 · Cited by 583 · see citing works
Self-citationShaham, O., Wei, R., Wang, T. J., Ricciardi, C., Lewis, G. D., Vasan, R. S., Carr, S. A., Thadhani, R., Gerszten, R. E., & Mootha, V. K. (2008) · Molecular Systems Biology · doi:10.1038/msb.2008.50 · Cited by 399 · see citing works
Soga, T., Ohishi, T., Matsui, T., Saito, T., Matsumoto, M., Takasaki, J., Matsumoto, S., Kamohara, M., Hiyama, H., Yoshida, S., et al. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.11.120 · Cited by 367 · see citing works
Sato, H., Macchiarulo, A., Thomas, C., Gioiello, A., Une, M., Hofmann, A. F., Saladin, R., Schoonjans, K., Pellicciari, R., & Auwerx, J. H. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm7015864 · Cited by 302 · see citing works
Self-citationChu, Z., Jones, R. M., He, H., Carroll, C., Gutierrez, V., Lucman, A., Moloney, M. K., Gao, H., Mondala, H., Bagnol, D., et al. (2007) · Endocrinology · doi:10.1210/en.2006-1608 · Cited by 295 · see citing works
Glucose-Sensing in Glucagon-Like Peptide-1-Secreting Cells
Reimann, F. M., & Gribble, F. M. (2002) · Diabetes · doi:10.2337/diabetes.51.9.2757 · Cited by 293 · see citing works
Extrapancreatic incretin receptors modulate glucose homeostasis, body weight, and energy expenditure
Hansotia, T., Maida, A., Flock, G., Yamada, Y., Tsukiyama, K., Seino, Y., & Drucker, D. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci25483 · Cited by 290 · see citing works
The Role of Voltage-Gated Calcium Channels in Pancreatic β-Cell Physiology and Pathophysiology
Yang, S.-N., & Berggren, P. (2006) · Endocrine Reviews · doi:10.1210/er.2005-0888 · Cited by 264 · see citing works
Durán-Sandoval, D., Cariou, B., Percevault, F., Hennuyer, N., Grefhorst, A., van Dijk, T. H., Gonzalez, F. J., Fruchart, J., Kuipers, F., & Staels, B. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m501931200 · Cited by 241 · see citing works
Hepatic Uptake of Bile Acids in Man
Angelin, B., Björkhem, I., Einarsson, K., & Ewerth, S. (1982) · Journal of Clinical Investigation · doi:10.1172/jci110668 · Cited by 222 · see citing works
FXR signaling in metabolic disease
Zhang, Y., & Edwards, P. A. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.11.015 · Cited by 209 · see citing works
Intestinal Epithelial Cells Synthesize Glucocorticoids and Regulate T Cell Activation
Cima, I., Corazza, N., Dick, B., Fuhrer, A. C., Herren, S., Jakob, S., Ayuni, E., Mueller, C., & Brunner, T. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031958 · Cited by 200 · see citing works
Mataki, C., Magnier, B. C., Houten, S. M., Annicotte, J., Argmann, C., Thomas, C., Overmars, H., Kulik, W., METZGER, D., Auwerx, J. H., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00852-07 · Cited by 141 · see citing works
Self-citationEvaluation of Glucose Homeostasis
Heikkinen, S., Argmann, C., Champy, M., & Auwerx, J. H. (2007) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb29b03s77 · Cited by 125 · see citing works
Self-citationPellicciari, R., Sato, H., Gioiello, A., Costantino, G., Macchiarulo, A., Sadeghpour, B. M., Giorgi, G., Schoonjans, K., & Auwerx, J. H. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm070633p · Cited by 105 · see citing works
Self-citationSakamoto, Y., Inoue, H., Kawakami, S., Miyawaki, K., Miyamoto, T., Mizuta, K., & Itakura, M. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.076 · Cited by 100 · see citing works
Impaired pancreatic growth, β cell mass, and β cell function in E2F1 –/– mice
Lluis Fajas, A., Annicotte, J., Miard, S., Sarruf, D. A., 渡辺, 光., & Auwerx, J. H. (2004) · Journal of Clinical Investigation · doi:10.1172/jci18555 · Cited by 99 · see citing works
Self-citationReimann, F. M., Maziarz, M., Flock, G. B., Habib, A. M., Drucker, D. J., & Gribble, F. M. (2004) · The Journal of Physiology · doi:10.1113/jphysiol.2004.076414 · Cited by 71 · see citing works
Histopathology in Mouse Metabolic Investigations
Mark, M. P., Teletin, M., Antal, M. C., Wendling, O., Auwerx, J. H., Heikkinen, S., Khetchoumian, K., Argmann, C., & Dgheem, M. (2007) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb29b04s78 · Cited by 44 · see citing works
Self-citationArgmann, C., Houten, S. M., Champy, M., & Auwerx, J. H. (2006) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb29b02s75 · Cited by 33 · see citing works
Self-citationCollection of Blood and Plasma from the Mouse
Argmann, C., & Auwerx, J. H. (2006) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb29a03s75 · Cited by 32 · see citing works
Self-citationMacchiarulo, A., Gioiello, A., Thomas, C., Massarotti, A., Nuti, R., Rosatelli, E., Sabbatini, P., Schoonjans, K., Auwerx, J. H., & Pellicciari, R. (2008) · Journal of Chemical Information and Modeling · doi:10.1021/ci800196h · Cited by 27 · see citing works
Self-citationDietary Manipulation of Mouse Metabolism
Feige, J. N., Lagouge, M., & Auwerx, J. (2008) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb29b05s84 · Cited by 18 · see citing works
Self-citationEvaluation of Energy Homeostasis
Argmann, C., Champy, M., & Auwerx, J. H. (2006) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb29b01s73 · Cited by 16 · see citing works
Self-citationMinimizing Variation Due to Genotype and Environment
Argmann, C., & Auwerx, J. H. (2006) · Current Protocols in Molecular Biology · doi:10.1002/0471142727.mb29a02s73 · Cited by 6 · see citing works
Self-citation
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Cryan, J. F., O'Riordan, K. J., Cowan, C. S. M., Sandhu, K. V., Bastiaanssen, T. F. S., Boehme, M., Codagnone, M. G., Cussotto, S., Fulling, C., Golubeva, A. V., et al. (2019) · Physiological Reviews · doi:10.1152/physrev.00018.2018 · Cited by 5,286 · see citing works
Gut microbiota in human metabolic health and disease
Fan, Y., & Pedersen, O. (2021) · Nature Reviews Microbiology · doi:10.1038/s41579-020-0433-9 · Cited by 4,724 · see citing works
Functional interactions between the gut microbiota and host metabolism
Tremaroli, V., & Bäckhed, F. (2012) · Nature · doi:10.1038/nature11552 · Cited by 4,387 · see citing works
Intestinal Crosstalk between Bile Acids and Microbiota and Its Impact on Host Metabolism
Wahlstrom, A. M., Sayin, S. I., Marschall, H., & Bäckhed, F. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.005 · Cited by 2,903 · see citing works
Thyroid Hormone Regulation of Metabolism
Mullur, R., Liu, Y.-Y., & Brent, G. A. (2014) · Physiological Reviews · doi:10.1152/physrev.00030.2013 · Cited by 2,421 · see citing works
Fuller, N. R., Colagiuri, S., SCHOFIELD, D. J., Olson, A. D., Shrestha, R. N., Holzapfel, C., Wolfenstetter, S. B., Holle, R., Ahern, A. L., Hauner, H., et al. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.139 · Cited by 2,125 · see citing works
Inflammation in obesity, diabetes, and related disorders
Rohm, T. V., Meier, D. T., Olefsky, J. M., & Donath, M. Y. (2022) · Immunity · doi:10.1016/j.immuni.2021.12.013 · Cited by 2,066 · see citing works
Mechanisms and disease consequences of nonalcoholic fatty liver disease
Loomba, R., Friedman, S. L., & Shulman, G. I. (2021) · Cell · doi:10.1016/j.cell.2021.04.015 · Cited by 2,002 · see citing works
Gut microbiota in cardiovascular health and disease
Tang, W. H. W., Kitai, T., & Hazen, S. L. (2017) · Circulation Research · doi:10.1161/circresaha.117.309715 · Cited by 1,670 · see citing works
The gut-liver axis and the intersection with the microbiome
Tripathi, A., Debelius, J., Brenner, D. A., Karin, M., Loomba, R., Schnabl, B., & Knight, R. (2018) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-018-0011-z · Cited by 1,480 · see citing works
Signals from the gut microbiota to distant organs in physiology and disease
Schroeder, B. O., & Bäckhed, F. (2016) · Nature Medicine · doi:10.1038/nm.4185 · Cited by 1,409 · see citing works
Bile Acid Metabolism and Signaling
Chiang, J. Y. L. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120023 · Cited by 1,390 · see citing works
Martin, C. R., Osadchiy, V., Kalani, A., & Mayer, E. A. (2018) · Cellular and Molecular Gastroenterology and Hepatology · doi:10.1016/j.jcmgh.2018.04.003 · Cited by 1,284 · see citing works
Bile acids and the gut microbiota: metabolic interactions and impacts on disease
Collins, S. L., Stine, J. G., Bisanz, J. E., Okafor, C. D., & Patterson, A. D. (2023) · Nature Reviews Microbiology · doi:10.1038/s41579-022-00805-x · Cited by 1,214 · see citing works
Pleiotropic Roles of Bile Acids in Metabolism
de Aguiar Vallim, T. Q., Tarling, E. J., & Edwards, P. A. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2013.03.013 · Cited by 1,209 · see citing works
Wang, K., Liao, M., Zhou, N., Bao, L., Ma, K., Zheng, Z., Wang, Y., Liu, C., Wang, W., Wang, J., et al. (2019) · Cell Reports · doi:10.1016/j.celrep.2018.12.028 · Cited by 1,166 · see citing works
Dietary lipids, gut microbiota and lipid metabolism
Schoeler, M., & Caesar, R. (2019) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-019-09512-0 · Cited by 1,163 · see citing works
The gut microbiota at the intersection of diet and human health
Gentile, C. L., & Weir, T. L. (2018) · Science · doi:10.1126/science.aau5812 · Cited by 1,049 · see citing works
Interactions Between the Intestinal Microbiome and Liver Diseases
Schnabl, B., & Brenner, D. A. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.01.020 · Cited by 971 · see citing works
Chávez-Talavera, O., Tailleux, A., Lefebvre, P., & Staels, B. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.055 · Cited by 970 · see citing works
Antibiotics and the Human Gut Microbiome: Dysbioses and Accumulation of Resistances
Francino, M. P. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2015.01543 · Cited by 956 · see citing works
Bile acid signaling in metabolic disease and drug therapy
Li, T., & Chiang, J. Y. L. (2014) · Pharmacological Reviews · doi:10.1124/pr.113.008201 · Cited by 935 · see citing works
Lipotoxicity and the gut-liver axis in NASH pathogenesis
Marra, F., & Svegliati-Baroni, G. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2017.11.014 · Cited by 847 · see citing works
Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome
Guo, C., Xie, S., Chi, Z., Zhang, J., Liu, Y., Zhang, L., Zheng, M., Zhang, X., Xia, D., Ke, Y., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.09.008 · Cited by 838 · see citing works
Linking Gut Microbiota and Inflammation to Obesity and Insulin Resistance
Saad, M. J. A., Santos, A., & Prada, P. O. (2016) · Physiology · doi:10.1152/physiol.00041.2015 · Cited by 818 · see citing works
Obesity and type 2 diabetes mellitus: connections in epidemiology, pathogenesis, and treatments
Ruze, R., Liu, T., Zou, X., Song, J., Chen, Y., Xu, R., Yin, X., & Xu, Q. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1161521 · Cited by 799 · see citing works
Metabolic Flexibility as an Adaptation to Energy Resources and Requirements in Health and Disease
Smith, R. L., Soeters, M. R., Wüst, R. C. I., & Houtkooper, R. H. (2018) · Endocrine Reviews · doi:10.1210/er.2017-00211 · Cited by 787 · see citing works
Jiao, N., Baker, S. S., Chapa-Rodriguez, A., Liu, W., Nugent, C. A., Tsompana, M., Mastrandrea, L., Buck, M. J., Baker, R. D., Genco, R. J., et al. (2018) · Gut · doi:10.1136/gutjnl-2017-314307 · Cited by 737 · see citing works
The human gut microbiota: Metabolism and perspective in obesity
Gomes, A. C., Hoffmann, C., & Mota, J. F. (2018) · Gut Microbes · doi:10.1080/19490976.2018.1465157 · Cited by 745 · see citing works
Metformin and the gastrointestinal tract
McCreight, L. J., Bailey, C. J., & Pearson, E. R. (2016) · Diabetologia · doi:10.1007/s00125-015-3844-9 · Cited by 733 · see citing works
Systemic gut microbial modulation of bile acid metabolism in host tissue compartments
Swann, J. R., Want, E. J., Geier, F. M., Spagou, K., Wilson, I. D., Sidaway, J. E., Nicholson, J. K., & Holmes, E. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1006734107 · Cited by 726 · see citing works
Adipose tissue in control of metabolism
Luo, L., & Liu, M. (2016) · Journal of Endocrinology · doi:10.1530/joe-16-0211 · Cited by 707 · see citing works
Bile acid receptors as targets for drug development
Schaap, F. G., Trauner, M., & Jansen, P. L. M. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.151 · Cited by 696 · see citing works
Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus
Foretz, M., Guigas, B., & Viollet, B. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0242-2 · Cited by 686 · see citing works
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Gribble, F. M., & Reimann, F. (2016) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021115-105439 · Cited by 683 · see citing works
Metabolites as regulators of insulin sensitivity and metabolism
Yang, Q., Vijayakumar, A., & Kahn, B. B. (2018) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0044-8 · Cited by 681 · see citing works
Bile acids and nonalcoholic fatty liver disease: Molecular insights and therapeutic perspectives
Arab, J. P., Karpen, S. J., Dawson, P. A., Arrese, M., & Trauner, M. (2017) · Hepatology · doi:10.1002/hep.28709 · Cited by 634 · see citing works
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Pols, T. W. H., Nomura, M., Harach, T., Sasso, G. L., Oosterveer, M. H., Thomas, C., Rizzo, G., Gioiello, A., Adorini, L., Pellicciari, R., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.11.006 · Cited by 622 · see citing works
Self-citationThe microbiota-gut-brain axis in obesity.
Torres-Fuentes, C., Schellekens, H., Dinan, T., & Cryan, J. (2017) · The Lancet Gastroenterology and Hepatology · doi:10.1016/s2468-1253(17)30147-4 · Cited by 506 · see citing works
Cellular bioenergetics as a target for obesity therapy
Tseng, Y.-H., Cypess, A. M., & Kahn, C. R. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3138 · Cited by 591 · see citing works
Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity
Vrieze, A., Out, C., Fuentes, S., Jonker, L., Reuling, I. J., Kootte, R. S., van Nood, E., Holleman, F., Knaapen, M., Romijn, J. A., et al. (2013) · Journal of Hepatology · doi:10.1016/j.jhep.2013.11.034 · Cited by 583 · see citing works
Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy
Chiang, J. Y. L., & Ferrell, J. M. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00223.2019 · Cited by 580 · see citing works
Steinert, R. E., Feinle-Bisset, C., Asarian, L., Horowitz, M., Beglinger, C., & Geary, N. (2017) · Physiological Reviews · doi:10.1152/physrev.00031.2014 · Cited by 578 · see citing works
Recent insights into the pathogenesis of nonalcoholic fatty liver disease
Arab, J. P., Arrese, M., & Trauner, M. (2018) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043617 · Cited by 573 · see citing works
Pathak, P., Xie, C., Nichols, R. G., Ferrell, J. M., Boehme, S., Krausz, K. W., Patterson, A. D., Gonzalez, F. J., & Chiang, J. Y. L. (2018) · Hepatology · doi:10.1002/hep.29857 · Cited by 567 · see citing works
The impact of the gut microbiota on the reproductive and metabolic endocrine system
Qi, X., Yun, C., Pang, Y., & Qiao, J. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1894070 · Cited by 573 · see citing works
Fleishman, J. S., & Kumar, S. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01811-6 · Cited by 577 · see citing works
Bile Acid Metabolism in Liver Pathobiology
Chiang, J. Y. L., & Ferrell, J. M. (2018) · Gene Expression · doi:10.3727/105221618x15156018385515 · Cited by 552 · see citing works
Furness, J. B., Rivera, L. R., Cho, H., Bravo, D. M., & Callaghan, B. P. (2013) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.180 · Cited by 549 · see citing works
Bile acid metabolism and signaling, the microbiota, and metabolic disease
Cai, J., Rimal, B., Jiang, C., Chiang, J. Y. L., & Patterson, A. D. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108238 · Cited by 513 · see citing works
Role of bile acids and their receptors in gastrointestinal and hepatic pathophysiology
Fuchs, C. D., & Trauner, M. (2022) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00566-7 · Cited by 490 · see citing works
Wang, Y., Chen, W., Yu, D. D., FORMAN, B. M., & Huang, W. (2011) · Hepatology · doi:10.1002/hep.24525 · Cited by 488 · see citing works
Molecular physiology of bile acid signaling in health, disease, and aging
Perino, A., Demagny, H., Velazquez-Villegas, L., & Schoonjans, K. (2021) · Physiological Reviews · doi:10.1152/physrev.00049.2019 · Cited by 481 · see citing works
Self-citationBile acid nuclear receptor FXR and digestive system diseases
Ding, L., Yang, L., Wang, Z., & Huang, W. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.01.004 · Cited by 477 · see citing works
The Intestinal Immune System in Obesity and Insulin Resistance
Winer, D. A., Luck, H., Tsai, S. J., & Winer, S. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.01.003 · Cited by 476 · see citing works
The bile acid TGR5 membrane receptor: from basic research to clinical application
Duboc, H., Taché, Y., & Hofmann, A. F. (2014) · Digestive and Liver Disease · doi:10.1016/j.dld.2013.10.021 · Cited by 473 · see citing works
Bile acids in glucose metabolism in health and disease
Shapiro, H., Kolodziejczyk, A. A., Halstuch, D., & Elinav, E. (2018) · The Journal of Experimental Medicine · doi:10.1084/jem.20171965 · Cited by 467 · see citing works
Zheng, X., Chen, T., Jiang, R., Zhao, A., Wu, Q., Kuang, J., Han, X., Li, M., Li, M., 黄凤杰, et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.11.017 · Cited by 464 · see citing works
Microbiota-gut-brain axis: Modulator of host metabolism and appetite
van de Wouw, M., Schellekens, H., Dinan, T. G., & Cryan, J. F. (2017) · The Journal of Nutrition · doi:10.3945/jn.116.240481 · Cited by 461 · see citing works
Beyond intestinal soap—bile acids in metabolic control
Kuipers, F., Bloks, V. W., & Groen, A. K. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.60 · Cited by 453 · see citing works
The bile acid membrane receptor TGR5 as an emerging target in metabolism and inflammation
Pols, T. W. H., Noriega, L. G., Nomura, M., Auwerx, J., & Schoonjans, K. (2011) · Journal of Hepatology · doi:10.1016/j.jhep.2010.12.004 · Cited by 454 · see citing works
Self-citationRole of bile acids in metabolic control
Molinaro, A., Wahlström, A., & Marschall, H.-U. (2018) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2017.11.002 · Cited by 447 · see citing works
Bile Acids as Metabolic Regulators and Nutrient Sensors
Chiang, J. Y. L., & Ferrell, J. M. (2019) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-082018-124344 · Cited by 440 · see citing works
The Gut Microbial Endocrine Organ: Bacterially Derived Signals Driving Cardiometabolic Diseases
Brown, J. M., & Hazen, S. L. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-060513-093205 · Cited by 438 · see citing works
Hormonal regulation of hepatic glucose production in health and disease
Lin, H. V., & Accili, D. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.06.003 · Cited by 429 · see citing works
Puri, P., Daita, K., Joyce, A., Mirshahi, F., Santhekadur, P. K., Cazanave, S., Luketic, V. A., Siddiqui, M. S., Boyett, S., Min, H., et al. (2018) · Hepatology · doi:10.1002/hep.29359 · Cited by 426 · see citing works
Role of the Microbiome in Energy Regulation and Metabolism
Nieuwdorp, M., Gilijamse, P. W., Pai, N., & Kaplan, L. M. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.02.008 · Cited by 421 · see citing works
Bile Acids Signal via TGR5 to Activate Intestinal Stem Cells and Epithelial Regeneration
Sorrentino, G., Perino, A., Yıldız, E., Alam, G. E., Sleiman, M. S. B., Gioiello, A., Pellicciari, R., & Schoonjans, K. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.05.067 · Cited by 409 · see citing works
Self-citationFarnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells
Trabelsi, M.-S., Daoudi, M., Prawitt, J., Ducastel, S., Touche, V., Sayin, S. I., Perino, A., Brighton, C. A., Sebti, Y., Kluza, J., et al. (2015) · Nature Communications · doi:10.1038/ncomms8629 · Cited by 402 · see citing works
Self-citationBile acid transporters and regulatory nuclear receptors in the liver and beyond
Halilbasic, E., Claudel, T., & Trauner, M. A. (2012) · Journal of Hepatology · doi:10.1016/j.jhep.2012.08.002 · Cited by 397 · see citing works
The TGR5 receptor mediates bile acid–induced itch and analgesia
Alemi, F., Kwon, E., Poole, D. P., Lieu, T., Lyo, V., Cattaruzza, F., Cevikbas, F., Steinhoff, M. S., Nassini, R., Materazzi, S., et al. (2013) · Journal of Clinical Investigation · doi:10.1172/jci64551 · Cited by 380 · see citing works
Self-citationGut microbiota, enteroendocrine functions and metabolism
Cani, P. D., Everard, A., & Duparc, T. (2013) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2013.09.008 · Cited by 378 · see citing works
Brown fat as a therapy for obesity and diabetes
Cypess, A. M., & Kahn, C. R. (2010) · Current Opinion in Endocrinology, Diabetes & Obesity · doi:10.1097/med.0b013e328337a81f · Cited by 376 · see citing works
Luo, P., Yin, P., Hua, R., Tan, Y., Li, Z., Qiu, G., Yin, Z., Xie, X., Wang, X., Chen, W., et al. (2017) · Hepatology · doi:10.1002/hep.29561 · Cited by 373 · see citing works
The UDP-Glycosyltransferase (UGT) Superfamily: New Members, New Functions, and Novel Paradigms
Meech, R., Hu, D. G., McKinnon, R. A., Mubarokah, S. N., Haines, A. Z., Nair, P. C., Rowland, A., & Mackenzie, P. I. (2019) · Physiological Reviews · doi:10.1152/physrev.00058.2017 · Cited by 363 · see citing works
Alemi, F., Poole, D. P., Chiu, J., Schoonjans, K., Cattaruzza, F., Grider, J. R., Bunnett, N. W., & Corvera, C. U. (2013) · Gastroenterology · doi:10.1053/j.gastro.2012.09.055 · Cited by 362 · see citing works
Self-citationHofmann, A. F., & Hagey, L. R. (2014) · Journal of Lipid Research · doi:10.1194/jlr.r049437 · Cited by 360 · see citing works
Environmental Factors, Gut Microbiota, and Colorectal Cancer Prevention
Song, M., & Chan, A. T. (2019) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2018.07.012 · Cited by 355 · see citing works
Brighton, C. A., Rievaj, J., Kuhre, R. E., Glasssmith, L. L., Schoonjans, K., Holst, J. J., Gribble, F. M., & Reimann, F. M. (2015) · Endocrinology · doi:10.1210/en.2015-1321 · Cited by 355 · see citing works
Self-citationThe therapeutic potential of manipulating gut microbiota in obesity and type 2 diabetes mellitus
Kootte, R. S., Vrieze, A., Holleman, F., Dallinga‐Thie, G. M., Zoetendal, E. G., de Vos, W. M., Groen, A. K., Hoekstra, J. B. L., Stroes, E. S. G., & Nieuwdorp, M. (2011) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2011.01483.x · Cited by 348 · see citing works
The migrating motor complex: control mechanisms and its role in health and disease
Deloose, E., Janssen, P., Depoortere, I., & Tack, J. F. (2012) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2012.57 · Cited by 350 · see citing works
Gut microbiome and its role in obesity and insulin resistance
Lee, C. J., Sears, C. L., & Maruthur, N. M. (2019) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.14107 · Cited by 352 · see citing works
Bile acids in glucose metabolism and insulin signalling — mechanisms and research needs
Ahmad, T. R., & Haeusler, R. A. (2019) · Nature Reviews Endocrinology · doi:10.1038/s41574-019-0266-7 · Cited by 342 · see citing works
Altered Bile Acid Metabolome in Patients with Nonalcoholic Steatohepatitis
Ferslew, B. C., Xie, G., Johnston, C., Su, M., Stewart, P. W., Jia, W. P., Brouwer, K. L. R., & Barritt, A. S. (2015) · Digestive Diseases and Sciences · doi:10.1007/s10620-015-3776-8 · Cited by 336 · see citing works
Internal senses of the vagus nerve
Prescott, S. L., & Liberles, S. D. (2022) · Neuron · doi:10.1016/j.neuron.2021.12.020 · Cited by 332 · see citing works
Farnesoid X Receptor Deficiency Improves Glucose Homeostasis in Mouse Models of Obesity
Prawitt, J., Abdelkarim, M., Stroeve, J. H. M., Popescu, I. R., Duez, H., Velagapudi, V., Dumont, J., Bouchaert, E., van Dijk, T. H., Lucas, A., et al. (2011) · Diabetes · doi:10.2337/db11-0030 · Cited by 327 · see citing works
Gut Microbiota: An Important Player in Type 2 Diabetes Mellitus
Zhou, Z., Sun, B., Yu, D., & Zhu, C. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.834485 · Cited by 346 · see citing works
Cyp2c70 is responsible for the species difference in bile acid metabolism between mice and humans
Takahashi, S., Fukami, T., Masuo, Y., Brocker, C. N., Xie, C., Krausz, K. W., Wolf, C. R., Henderson, C. J., & Gonzalez, F. J. (2016) · Journal of Lipid Research · doi:10.1194/jlr.m071183 · Cited by 314 · see citing works
The Gut Microbiome Influences Host Endocrine Functions
Rastelli, M., Cani, P. D., & Knauf, C. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00280 · Cited by 315 · see citing works
Gut Microbiota-Dependent Modulation of Energy Metabolism
Heiss, C. N., & Olofsson, L. E. (2018) · Journal of Innate Immunity · doi:10.1159/000481519 · Cited by 310 · see citing works
Bile Acids as Regulators of Hepatic Lipid and Glucose Metabolism
Trauner, M. A., Claudel, T., Fickert, P., Moustafa, T., & Wagner, M. (2010) · Digestive Diseases · doi:10.1159/000282091 · Cited by 310 · see citing works
Metabolic dysfunction-associated steatotic liver disease in adults
Huang, D. Q., Wong, V. W., Rinella, M. E., Boursier, J., Lazarus, J. V., Yki‐Järvinen, H., & Loomba, R. S. (2025) · Nature Reviews Disease Primers · doi:10.1038/s41572-025-00599-1 · Cited by 336 · see citing works
Heiss, C. N., & Olofsson, L. E. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12684 · Cited by 304 · see citing works
Effects of the gut microbiota on obesity and glucose homeostasis
Greiner, T. U., & Bäckhed, F. (2011) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2011.01.002 · Cited by 304 · see citing works
The gut microbiota and metabolic disease: current understanding and future perspectives
Arora, T., & Bäckhed, F. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12508 · Cited by 301 · see citing works
Bile acid metabolism and signaling in liver disease and therapy
Chiang, J. Y. L. (2017) · Liver Research · doi:10.1016/j.livres.2017.05.001 · Cited by 301 · see citing works
Role of Gut Microbiota in the Aetiology of Obesity: Proposed Mechanisms and Review of the Literature
Khan, M. J., Gerasimidis, K., Edwards, C. A., & Shaikh, M. G. (2016) · Journal of Obesity · doi:10.1155/2016/7353642 · Cited by 301 · see citing works
Up to date on cholesterol 7 alpha-hydroxylase (CYP7A1) in bile acid synthesis
Chiang, J. Y. L., & Ferrell, J. M. (2020) · Liver Research · doi:10.1016/j.livres.2020.05.001 · Cited by 303 · see citing works
Discovery of farnesoid X receptor and its role in bile acid metabolism
Chiang, J. Y. L., & Ferrell, J. M. (2022) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2022.111618 · Cited by 298 · see citing works
Paradigms of dynamic control of thyroid hormone signaling
Bianco, A. C., Dumitrescu, A., Gereben, B., Ribeiro, M. O., Fonseca, T. L., Fernandes, G. W., & Bocco, B. M. L. C. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00275 · Cited by 293 · see citing works
- Authors
- 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.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Perugia (IT)
- Intercept Pharmaceuticals (United States) (US)
- Corresponding author
- Auwerx, Johan
- Schoonjans, Kristina
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 10
- Issue
- 3
- Pages
- 167-177
- ISSN
- 1550-4131 (ISSN-L)
- PMC
- PMC2739652
- OpenAlex
- W2081271380
- Cited by
- 1,885
- References
- 43
- Citations by year
- 2026: 143 · 2025: 100 · 2024: 153 · 2023: 112 · 2022: 135 · 2021: 141 · 2020: 148 · 2019: 113 · 2018: 124 · 2017: 126 · 2016: 106 · 2015: 108 · 2014: 87 · 2013: 91 · 2012: 69
- FWCI
- 47.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1415 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Institut National de la Santé et de la Recherche Médicale
- European Commission
- Centre National de la Recherche Scientifique
- Australian Research Council
- National Institutes of Health
- Agence Nationale de la Recherche
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Health Sciences › Nursing › Nutrition and Dietetics › Biochemical Analysis and Sensing Techniques
- Keywords
- TGR5, glucose homeostasis, glucagon-like peptide-1, enteroendocrine cells, energy expenditure, diet-induced obesity, diabesity, ATP/ADP ratio, calcium mobilization, brown adipose tissue, pancreatic function, liver function, TGR5 agonists, INT-777, incretin-based therapy
- MeSH terms
- Adenosine Triphosphate, Animals, Bile Acids and Salts, Calcium, Cell Line, Cholic Acids, Cricetulus, Glucose, Cricetinae, Homeostasis, Humans, Insulin, Male, Mice, Inbred C57BL, Mice, Obese, Oxidative Phosphorylation, Signal Transduction, CHO Cells, Mice, Knockout, Enteroendocrine Cells, Receptors, G-Protein-Coupled, Mice, Glucagon-Like Peptide 1
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