Cited by 615

The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.

LXRS AND FXR: The Yin and Yang of Cholesterol and Fat Metabolism

Kalaany, Nada Y., Mangelsdorf, David J.·2006·Annual Review of Physiology

DOI 10.1146/annurev.physiol.68.033104.152158

Open this paper in CoChat — free account

Abstract

▪ Abstract Liver X receptors (LXRs) and farnesoid X receptor (FXR) are nuclear receptors that function as intracellular sensors for sterols and bile acids, respectively. In response to their ligands, these receptors induce transcriptional responses that maintain a balanced, finely tuned regulation of cholesterol and bile acid metabolism. LXRs also permit the efficient storage of carbohydrate- and fat-derived energy, whereas FXR activation results in an overall decrease in triglyceride levels and modulation of glucose metabolism. The elegant, dual interplay between these two receptor systems suggests that they coevolved to constitute a highly sensitive and efficient system for the maintenance of total body fat and cholesterol homeostasis. Emerging evidence suggests that the tissue-specific action of these receptors is also crucial for the proper function of the cardiovascular, immune, reproductive, endocrine pancreas, renal, and central nervous systems. Together, LXRs and FXR represent potential therapeutic targets for the treatment and prevention of numerous metabolic and lipid-related diseases.

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

Crossref · 10.1146/annurev.physiol.68.033104.152158

Cites

15 of 15 references verified0 citation errors · 0 not checkable

Statistics

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.

The coregulator exchange in transcriptional functions of nuclear receptors
Glass, C. K., & Rosenfeld, M. G. (2000) · Genes & Development · doi:10.1101/gad.14.2.121 · Cited by 2,233
The Enzymes, Regulation, and Genetics of Bile Acid Synthesis
Russell, D. W. (2003) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.72.121801.161712 · Cited by 2,069
9-cis retinoic acid is a high affinity ligand for the retinoid X receptor
Heyman, R. A., Mangelsdorf, D. J., Dyck, J. A., Stein, R. B., Eichele, G., Evans, R. M., & Thaller, C. (1992) · Cell · doi:10.1016/0092-8674(92)90479-v · Cited by 1,780
Self-citation
Endogenous Bile Acids Are Ligands for the Nuclear Receptor FXR/BAR
Wang, H., Chen, J., Hollister, K., Sowers, L. C., & Forman, B. M. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80348-2 · Cited by 1,636
Activation of the Nuclear Receptor LXR by Oxysterols Defines a New Hormone Response Pathway
Lehmann, J. M., Kliewer, S. A., Moore, L. B., Smith-Oliver, T. A., Oliver, B. B., Su, J.-L., Sundseth, S. S., Winegar, D. A., Blanchard, D. E., Spencer, T. A., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3137 · Cited by 1,233
Reciprocal regulation of inflammation and lipid metabolism by liver X receptors
Joseph, S. B., Castrillo, A., Laffitte, B. A., Mangelsdorf, D. J., & Tontonoz, P. (2003) · Nature Medicine · doi:10.1038/nm820 · Cited by 1,158
Self-citation
Regulation of multidrug resistance-associated protein 2 (ABCC2) by the nuclear receptors pregnane X receptor, farnesoid X-activated receptor, and constitutive androstane receptor
Kast, H. R., Goodwin, B., Tarr, P. T., Jones, S. A., Anisfeld, A. M., Stoltz, C. M., Tontonoz, P., Kliewer, S., Willson, T. M., & Edwards, P. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109326200 · Cited by 916
Diminished hepatic response to fasting/refeeding and liver X receptor agonists in mice with selective deficiency of sterol regulatory element-binding protein-1c
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
Prevention of atherosclerosis in apolipoprotein E-deficient mice by bone marrow transplantation
Linton, M. F., Atkinson, J. B., & Fazio, S. (1995) · Science · doi:10.1126/science.7863332 · Cited by 478
Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI: evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo
Ginsberg, H. N., Le, N. A., Goldberg, I. J., Gibson, J. C., Rubinstein, A., Wang-Iverson, P., Norum, R., & Brown, W. V. (1986) · Journal of Clinical Investigation · doi:10.1172/jci112713 · Cited by 424

Show all 15 references

Lipids and Lipid-Based Formulations: Optimizing the Oral Delivery of Lipophilic Drugs
Porter, C. J. H., Trevaskis, N. L., & Charman, W. N. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2197 · Cited by 1,824
High-Fat Diet Disrupts Behavioral and Molecular Circadian Rhythms in Mice
Kohsaka, A., Laposky, A. D., Ramsey, K. M., Estrada, C., Joshu, C., Kobayashi, Y., Turek, F. W., & Bass, J. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.006 · Cited by 1,528
Hepatic Fibroblast Growth Factor 21 Is Regulated by PPARα and Is a Key Mediator of Hepatic Lipid Metabolism in Ketotic States
Badman, M. K., Pissios, P., Kennedy, A. R., Koukos, G., Flier, J. S., & Maratos-Flier, E. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.05.002 · Cited by 1,495
Recent advances in 2D and 3D in vitro systems using primary hepatocytes, alternative hepatocyte sources and non-parenchymal liver cells and their use in investigating mechanisms of hepatotoxicity, cell signaling and ADME
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
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
Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation
Purushotham, A., Schug, T. T., Xu, Q., Surapureddi, S., Guo, X., & Li, X. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.02.006 · Cited by 1,003
Liver X receptors as integrators of metabolic and inflammatory signaling
Zelcer, N. (2006) · Journal of Clinical Investigation · doi:10.1172/jci27883 · Cited by 978
Lysosomal cholesterol activates mTORC1 via an SLC38A9–Niemann-Pick C1 signaling complex
Castellano, B. M., Thelen, A. M., Moldavski, O., Feltes, M., van der Welle, R. E. N., Mydock-McGrane, L., Jiang, X., van Eijkeren, R. J., Davis, O. B., Louie, S. M., et al. (2017) · Science · doi:10.1126/science.aag1417 · Cited by 562
Crosstalk between components of circadian and metabolic cycles in mammals
Asher, G., & Schibler, U. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.006 · Cited by 601
Regulation of Sterol Synthesis in Eukaryotes
Espenshade, P. J., & Hughes, A. L. (2007) · Annual Review of Genetics · doi:10.1146/annurev.genet.41.110306.130315 · Cited by 593
The Glia-Neuron Lactate Shuttle and Elevated ROS Promote Lipid Synthesis in Neurons and Lipid Droplet Accumulation in Glia via APOE/D
Liu, L., MacKenzie, K. R., Putluri, N., Maletić-Savatić, M., & Bellen, H. J. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.024 · Cited by 556
Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor
Yang, F., Huang, X., Yi, T., Yen, Y., Moore, D. D., & Huang, W. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-1078 · Cited by 488
Hepatic Insulin Resistance Is Sufficient to Produce Dyslipidemia and Susceptibility to Atherosclerosis
Biddinger, S. B., Hernandez-Ono, A., Rask-Madsen, C., Haas, J. T., Alemán, J. O., Suzuki, R., Scapa, E. F., Agarwal, C., Carey, M. C., Stephanopoulos, G., et al. (2008) · Cell Metabolism · doi:10.1016/j.cmet.2007.11.013 · Cited by 469
Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1
Rodgers, J. T., & Puigserver, P. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702509104 · Cited by 466
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
Endocrine fibroblast growth factors 15/19 and 21: from feast to famine
Potthoff, M. J., Kliewer, S. A., & Mangelsdorf, D. J. (2012) · Genes & Development · doi:10.1101/gad.184788.111 · Cited by 442
Self-citation
Targeting Sirtuin 1 to Improve Metabolism: All You Need Is NAD+?
Cantó, C., & Auwerx, J. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.003905 · Cited by 433
FXR, a multipurpose nuclear receptor
Lee, F. Y., Lee, H., Hubbert, M. L., Edwards, P. A., & Zhang, Y. (2006) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2006.08.002 · Cited by 344
FXR Acetylation Is Normally Dynamically Regulated by p300 and SIRT1 but Constitutively Elevated in Metabolic Disease States
Kemper, J. K., Xiao, Z., Ponugoti, B., Miao, J., Fang, S., Kanamaluru, D., Tsang, S., Wu, S.-Y., Chiang, C.-M., & Veenstra, T. D. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.09.009 · Cited by 332
Omega-3 Fatty Acids, Hepatic Lipid Metabolism, and Nonalcoholic Fatty Liver Disease
Scorletti, E., & Byrne, C. D. (2013) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071812-161230 · Cited by 326
Apolipoprotein E: From lipid transport to neurobiology
Hauser, P. S., Narayanaswami, V., & Ryan, R. O. (2011) · Progress in Lipid Research · doi:10.1016/j.plipres.2010.09.001 · Cited by 320
Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis
Worthmann, A., John, C., Rühlemann, M. C., Baguhl, M., Heinsen, F.-A., Schaltenberg, N., Heine, M., Schlein, C., Evangelakos, I., Mineo, C., et al. (2017) · Nature Medicine · doi:10.1038/nm.4357 · Cited by 318
Cholesterol 24-Hydroxylase: an enzyme of cholesterol turnover in the brain
Russell, D. W., Halford, R. W., Ramirez, D. M. O., Shah, R., & Kotti, T. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.072407.103859 · Cited by 317
Guts and Gall: Bile Acids in Regulation of Intestinal Epithelial Function in Health and Disease
Hegyi, P., Maléth, J., Walters, J. R., Hofmann, A. F., & Keely, S. J. (2018) · Physiological Reviews · doi:10.1152/physrev.00054.2017 · Cited by 269
The bile acid sensor farnesoid X receptor is a modulator of liver immunity in a rodent model of acute hepatitis
Mencarelli, A., Renga, B., Migliorati, M., Cipriani, S., Distrutti, E., Santucci, L., & Fiorucci, S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0901347 · Cited by 177
Liver X Receptor Agonist Treatment Ameliorates Amyloid Pathology and Memory Deficits Caused by High-Fat Diet in APP23 Mice
Fitz, N. F., Cronican, A., Pham, T., Fogg, A., Fauq, A. H., Chapman, R., Lefterov, I., & Koldamova, R. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1051-10.2010 · Cited by 175
Coupling of receptor conformation and ligand orientation determine graded activity
Bruning, J. B., Parent, A. A., Gil, G., Zhao, M., Nowak, J., Pace, M. C., Smith, C. L., Afonine, P. V., Adams, P. D., Katzenellenbogen, J. A., et al. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.451 · Cited by 142
ABCA1: at the nexus of cholesterol, HDL and atherosclerosis
ATTIE, A. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.02.001 · Cited by 126
Greasing the wheels of Aβ clearance in Alzheimer's Disease: The role of lipids and apolipoprotein E
Fan, J., Donkin, J., & Wellington, C. (2009) · BioFactors · doi:10.1002/biof.37 · Cited by 97
Hepatic Deletion of SIRT1 Decreases Hepatocyte Nuclear Factor 1 α/Farnesoid X Receptor Signaling and Induces Formation of Cholesterol Gallstones in Mice
Purushotham, A., Xu, Q., Lu, J., Foley, J. F., Yan, X., Kim, D.-H., Kemper, J. K., & Li, X. (2012) · Molecular and Cellular Biology · doi:10.1128/mcb.05988-11 · Cited by 87
Why lipids are important for Alzheimer disease?
Hirsch-Reinshagen, V., Burgess, B. L., & Wellington, C. L. (2009) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-008-0012-2 · Cited by 86
CYP46A1 Activation by Efavirenz Leads to Behavioral Improvement without Significant Changes in Amyloid Plaque Load in the Brain of 5XFAD Mice
Petrov, A. M., Lam, M., Mast, N., Moon, J., Li, Y., Maxfield, E., & Pikuleva, I. A. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00737-0 · Cited by 86
Lipid Metabolism and Glial Lipoproteins in the Central Nervous System
Hayashi, H. (2011) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.34.453 · Cited by 80
Fibroblast Growth Factor 19 Treatment Ameliorates Disruption of Hepatic Lipid Metabolism in Farnesoid X Receptor (Fxr)-Null Mice
Miyata, M., Sakaida, Y., Matsuzawa, H., Yoshinari, K., & Yamazoe, Y. (2011) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.34.1885 · Cited by 77
Cholesterol metabolism, apolipoprotein E, adenosine triphosphate-binding cassette transporters, and Alzheimer's disease
Hirsch-Reinshagen, V., & Wellington, C. L. (2007) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32813aeabf · Cited by 61
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
SIRT1 activator E1231 protects from experimental atherosclerosis and lowers plasma cholesterol and triglycerides by enhancing ABCA1 expression
Feng, T., Liu, P., Wang, X., Luo, J., Zuo, X., Jiang, X., Liu, C., Li, Y., Li, N., Chen, M., et al. (2018) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2018.04.039 · Cited by 35
Novel substituted isoxazole FXR agonists with cyclopropyl, hydroxycyclobutyl and hydroxyazetidinyl linkers: understanding and improving key determinants of pharmacological properties
Kinzel, O., Steeneck, C., Schlüter, T., Schulz, A., Gege, C., Hahn, U., Hambruch, E., Hornberger, M., Spalwisz, A., Frick, K., et al. (2016) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2016.05.070 · Cited by 35

Authors: Kalaany, N. Y., & Mangelsdorf, D. J.
Venue: Annual Review of Physiology
Publisher: Annual Reviews
Published: 2006-01-01
Volume: 68
Issue: 1
Pages: 159-191
ISSN: 0066-4278 (ISSN-L)
1545-1585
DOI: 10.1146/annurev.physiol.68.033104.152158
OpenAlex: W2155391879
Cited by: 615
References: 15
FWCI: 4.89
Type: journal article
Language: en
Open access: closed

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.

LXRS AND FXR: The Yin and Yang of Cholesterol and Fat Metabolism

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Self-check

Citations

Cites

Cited by

Metadata

Record

About these checks

Data sources