The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.
Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism
Open accessAbstract
The bile acid-activated receptors, nuclear farnesoid X receptor (FXR) and the membrane Takeda G-protein receptor 5 (TGR5), are known to improve glucose and insulin sensitivity in obese and diabetic mice. However, the metabolic roles of these two receptors and the underlying mechanisms are incompletely understood. Here, we studied the effects of the dual FXR and TGR5 agonist INT-767 on hepatic bile acid synthesis and intestinal secretion of glucagon-like peptide-1 (GLP-1) in wild-type, Fxr −/− , and Tgr5 −/− mice. INT-767 efficaciously stimulated intracellular Ca 2+ levels, cAMP activity, and GLP-1 secretion and improved glucose and lipid metabolism more than did the FXR-selective obeticholic acid and TGR5-selective INT-777 agonists. Interestingly, INT-767 reduced expression of the genes in the classic bile acid synthesis pathway but induced those in the alternative pathway, which is consistent with decreased taurocholic acid and increased tauromuricholic acids in bile. Furthermore, FXR activation induced expression of FXR target genes, including fibroblast growth factor 15, and unexpectedly Tgr5 and prohormone convertase 1/3 gene expression in the ileum. We identified an FXR-responsive element on the Tgr5 gene promoter. Fxr −/− and Tgr5 −/− mice exhibited reduced GLP-1 secretion, which was stimulated by INT-767 in the Tgr5 −/− mice but not in the Fxr −/− mice. Our findings uncovered a novel mechanism in which INT-767 activation of FXR induces Tgr5 gene expression and increases Ca 2+ levels and cAMP activity to stimulate GLP-1 secretion and improve hepatic glucose and lipid metabolism in high-fat diet-induced obese mice. Activation of both FXR and TGR5 may therefore represent an effective therapy for managing hepatic steatosis, obesity, and diabetes.
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Cites
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
TGR5-Mediated Bile Acid Sensing Controls Glucose Homeostasis
Thomas, C., Gioiello, A., Noriega, L., Strehle, A., Oury, J., Rizzo, G., Macchiarulo, A., Yamamoto, H., Mataki, C., Pruzanski, M., et al. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.08.001 · Cited by 1,885
Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., et al. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.09.001 · Cited by 1,865
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
Katsuma, S., Hirasawa, A., & Tsujimoto, G. (2005) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2005.01.139 · Cited by 789
Mojsov, S., Heinrich, G., Wilson, I. B., Ravazzola, M., Orci, L., & Habener, J. F. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)67324-7 · Cited by 724
Li, F., Jiang, C., Krausz, K. W., Li, Y., Albert, I., Hao, H., Fabre, K. M., Mitchell, J. B., Patterson, A. D., & Gonzalez, F. J. (2013) · Nature Communications · doi:10.1038/ncomms3384 · Cited by 705
Self-citationPatti, 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 · cited 1×
“In gastric bypass surgery of obese and diabetic patients, the rapid improvement of insulin sensitivity and glycemic control before weight reduction is positively correlated with increased serum bile acids and GLP-1 (37, 38).”
BackgroundHirschfield, G. M., Mason, A., Luketic, V., Lindor, K., Gordon, S. C., Mayo, M., Kowdley, K. V., Vincent, C., Bodhenheimer, H. C., Parés, A., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2014.12.005 · Cited by 576
Intestine-selective farnesoid X receptor inhibition improves obesity-related metabolic dysfunction
Jiang, C., Xie, C., Lv, Y., Li, J., Krausz, K. W., Shi, J., Brocker, C. N., Desai, D., Amin, S. G., Bisson, W. H., et al. (2015) · Nature Communications · doi:10.1038/ncomms10166 · Cited by 559
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Self-citationThe complex link between NAFLD and type 2 diabetes mellitus - mechanisms and treatments
Targher, G., Corey, K. E., Byrne, C. D., & Roden, M. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00448-y · Cited by 850
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
Self-citationPathak, 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
Self-citationMolecular 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
Metadata
- Authors
- Pathak, P., Liu, H., Boehme, S., Xie, C., Krausz, K. W., Gonzalez, F., & Chiang, J. Y. L.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2017-06
- Volume
- 292
- Issue
- 26
- Pages
- 11055-11069
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2610476879
- Cited by
- 253
- References
- 15
- FWCI
- 9.91
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Pathak, P., Liu, H., Boehme, S., Xie, C., Krausz, K. W., Gonzalez, F., & Chiang, J. Y. L. (2017). Farnesoid X receptor induces Takeda G-protein receptor 5 cross-talk to regulate bile acid synthesis and hepatic metabolism. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m117.784322
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