The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
The farnesoid X receptor modulates renal lipid metabolism and diet-induced renal inflammation, fibrosis, and proteinuria
Open accessAbstract
Diet-induced obesity is associated with proteinuria and glomerular disease in humans and rodents. We have shown that in mice fed a high-fat diet, increased renal expression of the transcriptional factor sterol-regulatory element binding protein-1 (SREBP-1) plays a critical role in renal lipid accumulation and increases the activity of proinflammatory cytokines and profibrotic growth factors. In the current study, we have determined a key role of the farnesoid X receptor (FXR) in modulating renal SREBP-1 activity, glomerular lesions, and proteinuria. We found that feeding a Western-style diet to DBA/2J mice results in proteinuria, podocyte loss, mesangial expansion, renal lipid accumulation, and increased expression of proinflammatory factors, oxidative stress, and profibrotic growth factors. Treatment of these mice with the highly selective and potent FXR-activating ligand 6-α-ethyl-chenodeoxycholic acid (INT-747) ameliorates triglyceride accumulation by modulating fatty acid synthesis and oxidation, improves proteinuria, prevents podocyte loss, mesangial expansion, accumulation of extracellular matrix proteins, and increased expression of profibrotic growth factors and fibrosis markers, and modulates inflammation and oxidative stress. Our results therefore indicate that FXR activation could represent an effective therapy for treatment of abnormal renal lipid metabolism with associated inflammation, oxidative stress, and kidney pathology in patients affected by obesity.
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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
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 · cited 2×
“It shows high bioavailability and limited off-target effects (45).”
BackgroundSelf-citationPellicciari, R., Fiorucci, S., Camaioni, E., Clerici, C., Costantino, G., Maloney, P. R., Morelli, A., Parks, D. J., & Willson, T. M. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm025529g · Cited by 743
Functional and Structural Changes in the Kidney in the Early Stages of Obesity
HENEGAR, J. R., BIGLER, S. A., HENEGAR, L. K., TYAGI, S. C., & HALL, J. E. (2001) · Journal of the American Society of Nephrology · doi:10.1681/asn.v1261211 · Cited by 549
Farnesoid x receptor ligands inhibit vascular smooth muscle cell inflammation and migration
Li, Y. T. Y., Swales, K. E., Thomas, G. J., Warner, T. D., & Bishop-Bailey, D. (2007) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.107.152694 · Cited by 171
Cited by
Godoy, P., Hewitt, N. J., Albrecht, U., Andersen, M. E., Ansari, N., Bhattacharya, S., Bode, J. G., Bolleyn, J., Borner, C., Böttger, J., et al. (2013) · Archives of Toxicology · doi:10.1007/s00204-013-1078-5 · Cited by 1,280
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
Mudaliar, S., Henry, R. R., Sanyal, A. J., Morrow, L., Marschall, H., Kipnes, M., Adorini, L., Sciacca, C. I., Clopton, P., Castelloe, E., et al. (2013) · Gastroenterology · doi:10.1053/j.gastro.2013.05.042 · Cited by 931
Self-citationTargeting fibrosis: mechanisms and clinical trials
Zhao, M., Wang, L., Wang, M., Zhou, S., Lu, Y., Cui, H., Racanelli, A. C., Zhang, L., Ye, T., Ding, B., et al. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01070-3 · Cited by 547
Inflammatory Links Between High Fat Diets and Diseases
Duan, Y., Zeng, L., Zheng, C., Song, B., Li, F., Kong, X., & Xu, K. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.02649 · Cited by 495
Metadata
- Authors
- Wang, X. X., Jiang, T., Shen, Y., Adorini, L., Pruzanski, M., Gonzalez, F. J., Scherzer, P., Lewis, L., Miyazaki-Anzai, S., & Levi, M.
- Venue
- American Journal of Physiology-Renal Physiology
- Publisher
- American Physiological Society
- Published
- 2009-12
- Volume
- 297
- Issue
- 6
- Pages
- F1587-F1596
- ISSN
- 1522-1466 (ISSN-L)
- 1931-857X
- OpenAlex
- W2125632718
- Cited by
- 178
- References
- 5
- FWCI
- 7.22
- Type
- journal article
- Language
- en
- Open access
- green
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- The paper
- Wang, X. X., Jiang, T., Shen, Y., Adorini, L., Pruzanski, M., Gonzalez, F. J., Scherzer, P., Lewis, L., Miyazaki-Anzai, S., & Levi, M. (2009). The farnesoid X receptor modulates renal lipid metabolism and diet-induced renal inflammation, fibrosis, and proteinuria. American Journal of Physiology-Renal Physiology. https://doi.org/10.1152/ajprenal.00404.2009
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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