The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
The Liver X Receptor (LXR) and Hepatic Lipogenesis
Open accessAbstract
The liver X receptors, LXRalpha (NR1H3) and LXRbeta (NR1H2), are ligand-activated transcription factors that belong to the nuclear hormone receptor superfamily. LXRs play a critical role in cholesterol homeostasis and bile acid metabolism. In addition, oral administration of LXR agonists to mice results in elevated hepatic fatty acid synthesis and steatosis and increased secretion of triglyceride-rich very low density lipoprotein resulting in hypertriglyceridemia. This increased hepatic lipogenesis has been largely attributed to the LXR-dependent up-regulation of sterol regulatory element-binding protein 1c (SREBP-1c) expression. However, it has been reported that treating Srebp-1c null mice with the synthetic LXR agonist T0901317 still results in enhanced expression of many lipogenic genes, suggesting additional mechanisms by which LXR can enhance hepatic lipogenesis. In this report, we identify the carbohydrate response element-binding protein (ChREBP) as an LXR target that independently enhances the up-regulation of select lipogenic genes. The ChREBP promoter contains functional LXR-binding sites that confer receptor-dependent binding and transactivation. We show that T0901317 treatment of mice is associated with up-regulation of the ChREBP target gene, liver-type pyruvate kinase. Therefore, activation of LXR not only increases ChREBP mRNA via enhanced transcription but also modulates ChREBP activity. This establishes LXR as a master lipogenic transcription factor, as it directly regulates both SREBP-1c and ChREBP to enhance hepatic fatty acid synthesis.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The nuclear receptor superfamily: the second decade
Mangelsdorf, D. J., Thummel, C., Beato, M., Herrlich, P., Schütz, G., Umesono, K., Blumberg, B., Kastner, P., Mark, M., Chambon, P., et al. (1995) · Cell · doi:10.1016/0092-8674(95)90199-x · Cited by 6,964
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
Liang, G., Yang, J., Horton, J. D., Hammer, R. E., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m111421200 · Cited by 669
Cited by
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
Liver X receptors in lipid signalling and membrane homeostasis
Wang, B., & Tontonoz, P. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0037-x · Cited by 722
Bile acids as regulatory molecules
Hylemon, P. B., Zhou, H., Pandak, W. M., Ren, S., Gil, G., & Dent, P. (2009) · Journal of Lipid Research · doi:10.1194/jlr.r900007-jlr200 · Cited by 694
Transcriptional regulation of hepatic lipogenesis
Wang, Y., Viscarra, J., Kim, S.-J., & Sul, H. S. (2015) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm4074 · Cited by 646
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
N-3 polyunsaturated fatty acid regulation of hepatic gene transcription
Jump, D. B. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e3282ffaf6a · Cited by 443
Increased very low density lipoprotein (VLDL) secretion, hepatic steatosis, and insulin resistance
Choi, S. H., & Ginsberg, H. N. (2011) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2011.04.007 · Cited by 418
Miyazaki, M., Flowers, M. T., Sampath, H., Chu, K., Otzelberger, C., Liu, X., & Ntambi, J. M. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.10.014 · Cited by 414
Thyroid hormone crosstalk with nuclear receptor signaling in metabolic regulation
Liu, Y.-Y., & Brent, G. A. (2010) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2009.11.004 · Cited by 218
Jamialahmadi, O., Mancina, R. M., Ciociola, E., Tavaglione, F., Luukkonen, P. K., Baselli, G., Malvestiti, F., Thuillier, D., Raverdy, V., Männistö, V., et al. (2021) · Gastroenterology · doi:10.1053/j.gastro.2020.12.023 · Cited by 148
Liver X receptors (LXR) as therapeutic targets in dyslipidemia
Bełtowski, J. (2008) · Cardiovascular Therapeutics · doi:10.1111/j.1755-5922.2008.00062.x · Cited by 132
Chronic social defeat stress disrupts regulation of lipid synthesis
Chuang, J.-C., Cui, H., Mason, B. L., Mahgoub, M., Bookout, A. L., Yu, H. G., Perello, M., Elmquist, J. K., Repa, J. J., Zigman, J. M., et al. (2010) · Journal of Lipid Research · doi:10.1194/jlr.m002196 · Cited by 126
Self-citationLipid metabolism and neuroinflammation in Alzheimer’s disease: a role for liver X receptors
Kang, J., & Rivest, S. (2012) · Endocrine Reviews · doi:10.1210/er.2011-1049 · Cited by 94
HDL-cholesterol and cardiovascular disease: rethinking our approach
Siddiqi, H. K., Kiss, D., & Rader, D. (2015) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000211 · Cited by 77
Gastric inhibitory polypeptide immunoneutralization attenuates development of obesity in mice
Boylan, M. O., Glazebrook, P. A., Tatalovic, M., & Wolfe, M. M. (2015) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00345.2015 · Cited by 65
Nuclear Receptors in Nonalcoholic Fatty Liver Disease
López-Velázquez, J. A., Carrillo-Córdova, L. D., Chávez-Tapia, N. C., Uribe, M., & Méndez-Sánchez, N. (2012) · Journal of Lipids · doi:10.1155/2012/139875 · Cited by 48
Liu, Y., Han, X., Bian, Z., Peng, Y., You, Z., Wang, Q., Chen, X., Qiu, D., & Ma, X. (2012) · Digestive Diseases and Sciences · doi:10.1007/s10620-011-1902-9 · Cited by 35
Wang, Y., Bendre, S. V., Krauklis, S. A., Steelman, A. J., & Nelson, E. R. (2025) · Endocrinology · doi:10.1210/endocr/bqaf031 · Cited by 6
Metadata
- Authors
- Cha, J.-Y., & Repa, J. J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2007-01
- Volume
- 282
- Issue
- 1
- Pages
- 743-751
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2009577529
- Cited by
- 470
- References
- 3
- FWCI
- 27.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
