Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Applied Bio

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 30 November 2001:
Vol. 294. no. 5548, pp. 1866 - 1870
DOI: 10.1126/science.294.5548.1866
Prev | Table of Contents | Next

Review

Nuclear Receptors and Lipid Physiology: Opening the X-Files

Ajay Chawla,1* Joyce J. Repa,2* Ronald M. Evans,1dagger David J. Mangelsdorf2dagger

Cholesterol, fatty acids, fat-soluble vitamins, and other lipids present in our diets are not only nutritionally important but serve as precursors for ligands that bind to receptors in the nucleus. To become biologically active, these lipids must first be absorbed by the intestine and transformed by metabolic enzymes before they are delivered to their sites of action in the body. Ultimately, the lipids must be eliminated to maintain a normal physiological state. The need to coordinate this entire lipid-based metabolic signaling cascade raises important questions regarding the mechanisms that govern these pathways. Specifically, what is the nature of communication between these bioactive lipids and their receptors, binding proteins, transporters, and metabolizing enzymes that links them physiologically and speaks to a higher level of metabolic control? Some general principles that govern the actions of this class of bioactive lipids and their nuclear receptors are considered here, and the scheme that emerges reveals a complex molecular script at work.

Nuclear receptors function as ligand-activated transcription factors that regulate the expression of target genes to affect processes as diverse as reproduction, development, and general metabolism. These proteins were first recognized as the mediators of steroid hormone signaling and provided an important link between transcriptional regulation and physiology. In the mid-1980s, the steroid receptors were cloned and found to exhibit extensive sequence similarity. The subsequent cloning of other receptor genes led to the unexpected discovery that there were many more nuclear receptor-like genes than previously suspected. Today, the human genome is reported to contain 48 members of this transcription factor family (1). This superfamily includes not only the classic endocrine receptors that mediate the actions of steroid hormones, thyroid hormones, and the fat-soluble vitamins A and D (2), but a large number of so-called orphan nuclear receptors, whose ligands, target genes, and physiological functions were initially unknown (3). Exciting progress has been made over the last several years to elucidate the role of these orphan receptors in animal biology. Here we review recent discoveries that suggest that unlike the classic endocrine nuclear hormone receptors, many of the orphan receptors function as lipid sensors that respond to cellular lipid levels and elicit gene expression changes to ultimately protect cells from lipid overload.

The structural organization of nuclear receptors is similar despite wide variation in ligand sensitivity (Fig. 1). With few exceptions, these proteins contain an NH2-terminal region that harbors a ligand-independent transcriptional activation function (AF-1); a core DNA-binding domain, containing two highly conserved zinc finger motifs that target the receptor to specific DNA sequences known as hormone response elements; a hinge region that permits protein flexibility to allow for simultaneous receptor dimerization and DNA binding; and a large COOH-terminal region that encompasses the ligand-binding domain, dimerization interface, and a ligand-dependent activation function (AF-2). Upon ligand binding, nuclear receptors undergo a conformational change that coordinately dissociates corepressors and facilitates recruitment of coactivator proteins to enable transcriptional activation (4).

The importance of nuclear receptors in maintaining the normal physiological state is illustrated by the enormous pharmacopoeia that has been developed to combat disorders that have inappropriate nuclear receptor signaling as a key pathological determinant. These disorders affect every field of medicine, including reproductive biology, inflammation, cancer, diabetes, cardiovascular disease, and obesity. Therefore, to maintain a normal physiological state, the spatial and temporal activity of nuclear receptors must be tightly controlled by tissue-specific expression of the receptors, as well as ligand availability. Interestingly, an evaluation of the pathways involved in ligand availability reveals the existence of two distinctly different nuclear receptor paradigms.

The first paradigm is represented by the classic nuclear steroid hormone receptors (Fig. 1). Members of this group include the glucocorticoid (GR), mineralocorticoid (MR), estrogen (ER), androgen (AR), and progesterone (PR) receptors. Steroid receptors bind to DNA as homodimers, and their ligands are synthesized exclusively from endogenous endocrine sources that are regulated by negative-feedback control of the hypothalamic-pituitary axis (5). After synthesis, steroid hormones are circulated in the body to their target tissues where they bind to their receptors with high affinity (dissociation constant Kd = 0.01 to 10 nM). In vertebrates, the steroid receptor system evolved to regulate a variety of crucial metabolic and developmental events, including sexual differentiation, reproduction, carbohydrate metabolism, and electrolyte balance. The endocrine steroid receptors, their ligands, and the pathways they regulate have been the subject of decades of research, and their mechanism of action is well documented (5).

The second nuclear receptor paradigm is represented by the adopted orphan nuclear receptors that function as heterodimers with the retinoid X receptor (RXR) (Fig. 1). Orphan receptors become adopted when they are shown to bind a physiological ligand. In contrast to the endocrine steroid receptors, the adopted orphan receptors respond to dietary lipids and, therefore, their concentrations cannot be limited by simple negative-feedback control (Fig. 2). Members of this group include receptors for fatty acids (PPARs), oxysterols (LXRs), bile acids (FXR), and xenobiotics [steroid xenobiotic receptor/pregnane X receptor (SXR/PXR) and constitutive androstane receptor (CAR)]. Furthermore, the receptors in this group bind their lipid ligands with lower affinities comparable to physiological concentrations that can be affected by dietary intake (>1 to 10 µM). An emerging theme regarding these receptors is that they function as lipid sensors. In keeping with this notion, ligand binding to each of these receptors activates a feedforward, metabolic cascade that maintains nutrient lipid homeostasis by governing the transcription of a common family of genes involved in lipid metabolism, storage, transport, and elimination.

In addition to the adopted orphan receptors, there are four other RXR heterodimer receptors that do not fit precisely into either the feedforward or feedback paradigms mentioned. These include the thyroid hormone (TR), retinoic acid (RAR), vitamin D (VDR), and ecdysone (EcR) receptors (6-9). The ligands for these four receptors and the pathways they regulate employ elements of both the endocrine and lipid-sensing receptor pathways. For example, like other RXR heterodimer ligands, both retinoic acid and ecdysone are derived from essential dietary lipids (vitamin A and cholesterol, respectively), yet they are not calorigenic and the transcriptional pathways that these ligands regulate (i.e., morphogenesis and development) more closely resemble those of the endocrine receptors. Likewise, vitamin D and thyroid hormone require exogenous elements for their synthesis (sunshine for vitamin D, iodine for thyroid hormone), yet the ultimate synthesis of these hormones and the pathways they regulate are under strict endocrine control. Thus, it is possible that these four receptors provide an evolutionary segue, spanning the gap between the endocrine receptors and the adopted orphan receptors that have recently been shown to be lipid sensors.

1 Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, Post Office Box 85800, San Diego, CA 92186-5800, USA.
2 Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9050, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: evans{at}salk.edu (R.M.E.); davo.mango{at}utsouthwestern.edu (D.J.M.)

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Minireview: Nuclear Receptors and Breast Cancer.
S. D. Conzen (2008)
Mol. Endocrinol. 22, 2215-2228
   Abstract »    Full Text »    PDF »
Research Resource: Nuclear Hormone Receptor Expression in the Endocrine Pancreas.
J.-C. Chuang, J.-Y. Cha, J. C. Garmey, R. G. Mirmira, and J. J. Repa (2008)
Mol. Endocrinol. 22, 2353-2363
   Abstract »    Full Text »    PDF »
The Emerging Role of Nuclear Receptor ROR{alpha} and Its Crosstalk with LXR in Xeno- and Endobiotic Gene Regulation.
T. Wada, H. S. Kang, A. M. Jetten, and W. Xie (2008)
Experimental Biology and Medicine 233, 1191-1201
   Abstract »    Full Text »    PDF »
Vitamin D Signaling, Infectious Diseases, and Regulation of Innate Immunity.
J. H. White (2008)
Infect. Immun. 76, 3837-3843
   Full Text »    PDF »
Increased Cellular Free Cholesterol in Macrophage-specific Abca1 Knock-out Mice Enhances Pro-inflammatory Response of Macrophages.
X. Zhu, J.-Y. Lee, J. M. Timmins, J. M. Brown, E. Boudyguina, A. Mulya, A. K. Gebre, M. C. Willingham, E. M. Hiltbold, N. Mishra, et al. (2008)
J. Biol. Chem. 283, 22930-22941
   Abstract »    Full Text »    PDF »
Retinoic Acid Decreases Adherence of Murine Myeloid Dendritic Cells and Increases Production of Matrix Metalloproteinase-9.
D. E. Lackey, S. L. Ashley, A. L. Davis, and K. A. Hoag (2008)
J. Nutr. 138, 1512-1519
   Abstract »    Full Text »    PDF »
Site-specific Androgen Receptor Serine Phosphorylation Linked to Epidermal Growth Factor-dependent Growth of Castration-recurrent Prostate Cancer.
L. A. Ponguta, C. W. Gregory, F. S. French, and E. M. Wilson (2008)
J. Biol. Chem. 283, 20989-21001
   Abstract »    Full Text »    PDF »
Endothelial Progenitor Cells and Angiogenesis Join the PPARty.
F. Biscetti and R. Pola (2008)
Circ. Res. 103, 7-9
   Full Text »    PDF »
Peroxisome Proliferator-Activated Receptors Mediate Host Cell Proinflammatory Responses to Pseudomonas aeruginosa Autoinducer.
A. Jahoor, R. Patel, A. Bryan, C. Do, J. Krier, C. Watters, W. Wahli, G. Li, S. C. Williams, and K. P. Rumbaugh (2008)
J. Bacteriol. 190, 4408-4415
   Abstract »    Full Text »    PDF »
Nuclear Receptors and Inflammatory Diseases.
K. Wang and Y.-J. Y. Wan (2008)
Experimental Biology and Medicine 233, 496-506
   Abstract »    Full Text »    PDF »
TRB3 suppresses adipocyte differentiation by negatively regulating PPAR{gamma} transcriptional activity.
Y. Takahashi, N. Ohoka, H. Hayashi, and R. Sato (2008)
J. Lipid Res. 49, 880-892
   Abstract »    Full Text »    PDF »
Induction of Apoptosis in Human Prostate Cancer Cells by Insulin-Like Growth Factor Binding Protein-3 Does Not Require Binding to Retinoid X Receptor-{alpha}.
G. Zappala, C. Elbi, J. Edwards, J. Gorenstein, M. M. Rechler, and N. Bhattacharyya (2008)
Endocrinology 149, 1802-1812
   Abstract »    Full Text »    PDF »
Nuclear Receptor Coactivator PNRC2 Regulates Energy Expenditure and Adiposity.
D. Zhou, R. Shen, J. J. Ye, Y. Li, W. Tsark, D. Isbell, P. Tso, and S. Chen (2008)
J. Biol. Chem. 283, 541-553
   Abstract »    Full Text »    PDF »
Nicotinamide Uncouples Hormone-Dependent Chromatin Remodeling from Transcription Complex Assembly.
S. Aoyagi and T. K. Archer (2008)
Mol. Cell. Biol. 28, 30-39
   Abstract »    Full Text »    PDF »
Fenofibrate reduces intestinal cholesterol absorption via PPAR{alpha}-dependent modulation of NPC1L1 expression in mouse.
M. A. Valasek, S. L. Clarke, and J. J. Repa (2007)
J. Lipid Res. 48, 2725-2735
   Abstract »    Full Text »    PDF »
CMO1 Deficiency Abolishes Vitamin A Production from beta-Carotene and Alters Lipid Metabolism in Mice.
S. Hessel, A. Eichinger, A. Isken, J. Amengual, S. Hunzelmann, U. Hoeller, V. Elste, W. Hunziker, R. Goralczyk, V. Oberhauser, et al. (2007)
J. Biol. Chem. 282, 33553-33561
   Abstract »    Full Text »    PDF »
Trans-10, cis-12 conjugated linoleic acid activates the integrated stress response pathway in adipocytes.
P. C. LaRosa, J.-J. M. Riethoven, H. Chen, Y. Xia, Y. Zhou, M. Chen, J. Miner, and M. E. Fromm (2007)
Physiol Genomics 31, 544-553
   Abstract »    Full Text »    PDF »
TNF-{alpha} interferes with lipid homeostasis and activates acute and proatherogenic processes.
K. F. Tacer, D. Kuzman, M. Seliskar, D. Pompon, and D. Rozman (2007)
Physiol Genomics 31, 216-227
   Abstract »    Full Text »    PDF »
Liver X Receptor-{alpha} Gene Expression Is Positively Regulated by Thyroid Hormone.
K. Hashimoto, S. Matsumoto, M. Yamada, T. Satoh, and M. Mori (2007)
Endocrinology 148, 4667-4675
   Abstract »    Full Text »    PDF »
Phosphorylation of Estrogen Receptor-{alpha} at Ser167 Is Indicative of Longer Disease-Free and Overall Survival in Breast Cancer Patients.
J. Jiang, N. Sarwar, D. Peston, E. Kulinskaya, S. Shousha, R. C. Coombes, and S. Ali (2007)
Clin. Cancer Res. 13, 5769-5776
   Abstract »    Full Text »    PDF »
The Xenobiotic-Sensing Nuclear Receptors Pregnane X Receptor, Constitutive Androstane Receptor, and Orphan Nuclear Receptor Hepatocyte Nuclear Factor 4{alpha} in the Regulation of Human Steroid-/Bile Acid-Sulfotransferase.
I. Echchgadda, C. S. Song, T. Oh, M. Ahmed, I. J. De La Cruz, and B. Chatterjee (2007)
Mol. Endocrinol. 21, 2099-2111
   Abstract »    Full Text »    PDF »
Estrogen Deprivation and Inhibition of Breast Cancer Growth in Vivo through Activation of the Orphan Nuclear Receptor Liver X Receptor.
H. Gong, P. Guo, Y. Zhai, J. Zhou, H. Uppal, M. J. Jarzynka, W.-C. Song, S.-Y. Cheng, and W. Xie (2007)
Mol. Endocrinol. 21, 1781-1790
   Abstract »    Full Text »    PDF »
Nuclear receptor ERR{alpha} and coactivator PGC-1beta are effectors of IFN-{gamma}-induced host defense.
J. Sonoda, J. Laganiere, I. R. Mehl, G. D. Barish, L.-W. Chong, X. Li, I. E. Scheffler, D. C. Mock, A. R. Bataille, F. Robert, et al. (2007)
Genes & Dev. 21, 1909-1920
   Abstract »    Full Text »    PDF »
Peroxisome Proliferator Activated Receptor {alpha}/{gamma} Dual Agonist Tesaglitazar Attenuates Diabetic Nephropathy in db/db Mice.
D. R. Cha, X. Zhang, Y. Zhang, J. Wu, D. Su, J. Y. Han, X. Fang, B. Yu, M. D. Breyer, and Y. Guan (2007)
Diabetes 56, 2036-2045
   Abstract »    Full Text »    PDF »
Receptor Interacting Protein 140 Regulates Expression of Uncoupling Protein 1 in Adipocytes through Specific Peroxisome Proliferator Activated Receptor Isoforms and Estrogen-Related Receptor {alpha}.
D. Debevec, M. Christian, D. Morganstein, A. Seth, B. Herzog, M. Parker, and R. White (2007)
Mol. Endocrinol. 21, 1581-1592
   Abstract »    Full Text »    PDF »
Selective Activation of Liver X Receptors by Acanthoic Acid-Related Diterpenes.
P. G. Traves, S. Hortelano, M. Zeini, T.-H. Chao, T. Lam, S. T. Neuteboom, E. A. Theodorakis, M. A. Palladino, A. Castrillo, and L. Bosca (2007)
Mol. Pharmacol. 71, 1545-1553
   Abstract »    Full Text »    PDF »
Nongenomic signaling of the retinoid X receptor through binding and inhibiting Gq in human platelets.
L. A. Moraes, K. E. Swales, J. A. Wray, A. Damazo, J. M. Gibbins, T. D. Warner, and D. Bishop-Bailey (2007)
Blood 109, 3741-3744
   Abstract »    Full Text »    PDF »
Block of Nuclear Receptor Ubiquitination: A MECHANISM OF LIGAND-DEPENDENT CONTROL OF PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR {delta} ACTIVITY.
D. Genini and C. V. Catapano (2007)
J. Biol. Chem. 282, 11776-11785
   Abstract »    Full Text »    PDF »
Liquid chromatography-mass spectrometry utilizing multi-stage fragmentation for the identification of oxysterols.
K. Karu, M. Hornshaw, G. Woffendin, K. Bodin, M. Hamberg, G. Alvelius, J. Sjovall, J. Turton, Y. Wang, and W. J. Griffiths (2007)
J. Lipid Res. 48, 976-987
   Abstract »    Full Text »    PDF »
Raloxifene and ICI182,780 Increase Estrogen Receptor-{alpha} Association with a Nuclear Compartment via Overlapping Sets of Hydrophobic Amino Acids in Activation Function 2 Helix 12.
M. Lupien, M. Jeyakumar, E. Hebert, K. Hilmi, D. Cotnoir-White, C. Loch, A. Auger, G. Dayan, G.-A. Pinard, J.-M. Wurtz, et al. (2007)
Mol. Endocrinol. 21, 797-816
   Abstract »    Full Text »    PDF »
Transactivation of a DR-1 PPRE by a human constitutive androstane receptor variant expressed from internal protein translation start sites.
M. A. Stoner, S. S. Auerbach, S. M. Zamule, S. C. Strom, and C. J. Omiecinski (2007)
Nucleic Acids Res. 35, 2177-2190
   Abstract »    Full Text »    PDF »
Peroxisome Proliferator-Activated Receptor-{alpha} Activation Inhibits Langerhans Cell Function.
S. Dubrac, P. Stoitzner, D. Pirkebner, A. Elentner, K. Schoonjans, J. Auwerx, S. Saeland, P. Hengster, P. Fritsch, N. Romani, et al. (2007)
J. Immunol. 178, 4362-4372
   Abstract »    Full Text »    PDF »
Pus3p- and Pus1p-Dependent Pseudouridylation of Steroid Receptor RNA Activator Controls a Functional Switch that Regulates Nuclear Receptor Signaling.
X. Zhao, J. R. Patton, S. K. Ghosh, N. Fischel-Ghodsian, L. Shen, and R. A. Spanjaard (2007)
Mol. Endocrinol. 21, 686-699
   Abstract »    Full Text »    PDF »
The Role of Extranuclear Signaling Actions of Progesterone Receptor in Mediating Progesterone Regulation of Gene Expression and the Cell Cycle.
V. Boonyaratanakornkit, E. McGowan, L. Sherman, M. A. Mancini, B. J. Cheskis, and D. P. Edwards (2007)
Mol. Endocrinol. 21, 359-375
   Abstract »    Full Text »    PDF »
The Liver X Receptor (LXR) and Hepatic Lipogenesis: THE CARBOHYDRATE-RESPONSE ELEMENT-BINDING PROTEIN IS A TARGET GENE OF LXR.
J.-Y. Cha and J. J. Repa (2007)
J. Biol. Chem. 282, 743-751
   Abstract »    Full Text »    PDF »
The Insulin-like Growth Factor-binding Protein 1 Gene Is a Primary Target of Peroxisome Proliferator-activated Receptors.
T. Degenhardt, M. Matilainen, K.-H. Herzig, T. W. Dunlop, and C. Carlberg (2006)
J. Biol. Chem. 281, 39607-39619
   Abstract »    Full Text »    PDF »
Identification of Biomarkers Modulated by the Rexinoid LGD1069 (Bexarotene) in Human Breast Cells Using Oligonucleotide Arrays.
H.-T. Kim, G. Kong, D. DeNardo, Y. Li, I. Uray, S. Pal, S. Mohsin, S. G. Hilsenbeck, R. Bissonnette, W. W. Lamph, et al. (2006)
Cancer Res. 66, 12009-12018
   Abstract »    Full Text »    PDF »
Overview of Nomenclature of Nuclear Receptors.
P. Germain, B. Staels, C. Dacquet, M. Spedding, and V. Laudet (2006)
Pharmacol. Rev. 58, 685-704
   Abstract »    Full Text »    PDF »
International Union of Pharmacology. LXIII. Retinoid X Receptors.
P. Germain, P. Chambon, G. Eichele, R. M. Evans, M. A. Lazar, M. Leid, A. R. De Lera, R. Lotan, D. J. Mangelsdorf, and H. Gronemeyer (2006)
Pharmacol. Rev. 58, 760-772
   Abstract »    Full Text »    PDF »
International Union of Pharmacology. LXVI. Orphan Nuclear Receptors.
G. Benoit, A. Cooney, V. Giguere, H. Ingraham, M. Lazar, G. Muscat, T. Perlmann, J.-P. Renaud, J. Schwabe, F. Sladek, et al. (2006)
Pharmacol. Rev. 58, 798-836
   Abstract »    Full Text »    PDF »
Peroxisome Proliferator-Activated Receptor-{gamma} Activates p53 Gene Promoter Binding to the Nuclear Factor-{kappa}B Sequence in Human MCF7 Breast Cancer Cells.
D. Bonofiglio, S. Aquila, S. Catalano, S. Gabriele, M. Belmonte, E. Middea, H. Qi, C. Morelli, M. Gentile, M. Maggiolini, et al. (2006)
Mol. Endocrinol. 20, 3083-3092
   Abstract »    Full Text »    PDF »
Regulation of hepatic cholesterol synthesis by a novel protein (SPF) that accelerates cholesterol biosynthesis.
N. Shibata, K.-i. Jishage, M. Arita, M. Watanabe, Y. Kawase, K. Nishikawa, Y. Natori, H. Inoue, H. Shimano, N. Yamada, et al. (2006)
FASEB J 20, 2642-2644
   Abstract »    Full Text »    PDF »
The NR4A Orphan Nuclear Receptor NOR1 Is Induced by Platelet-derived Growth Factor and Mediates Vascular Smooth Muscle Cell Proliferation.
T. Nomiyama, T. Nakamachi, F. Gizard, E. B. Heywood, K. L. Jones, N. Ohkura, R. Kawamori, O. M. Conneely, and D. Bruemmer (2006)
J. Biol. Chem. 281, 33467-33476
   Abstract »    Full Text »    PDF »
Regulation of peroxisome proliferator-activated receptor-{gamma} in liver fibrosis.
L. Yang, C.-C. Chan, O.-S. Kwon, S. Liu, J. McGhee, S. A. Stimpson, L. Z. Chen, W. W. Harrington, W. T. Symonds, and D. C. Rockey (2006)
Am J Physiol Gastrointest Liver Physiol 291, G902-G911
   Abstract »    Full Text »    PDF »
Type II nuclear hormone receptors, coactivator, and target gene repression in adipose tissue in the acute-phase response.
B. Lu, A. H. Moser, J. K. Shigenaga, K. R. Feingold, and C. Grunfeld (2006)
J. Lipid Res. 47, 2179-2190
   Abstract »    Full Text »    PDF »
Hypericum sampsonii induces apoptosis and nuclear export of retinoid X receptor-alpha.
J.-Z. Zeng, D.-F. Sun, L. Wang, X. Cao, J.-B. Qi, T. Yang, C.-Q. Hu, W. Liu, and X.-K. Zhang (2006)
Carcinogenesis 27, 1991-2000
   Abstract »    Full Text »    PDF »
Dynamic regulation of Drosophila nuclear receptor activity in vivo.
L. Palanker, A. S. Necakov, H. M. Sampson, R. Ni, C. Hu, C. S. Thummel, and H. M. Krause (2006)
Development 133, 3549-3562
   Abstract »    Full Text »    PDF »
Phosphorylation of ER{alpha} at serine 118 in primary breast cancer and in tamoxifen-resistant tumours is indicative of a complex role for ER{alpha} phosphorylation in breast cancer progression..
N Sarwar, J-S Kim, J Jiang, D Peston, H D Sinnett, P Madden, J M Gee, R I Nicholson, A E Lykkesfeldt, S Shousha, et al. (2006)
Endocr. Relat. Cancer 13, 851-861
   Abstract »    Full Text »    PDF »
Mouse Sterol Response Element Binding Protein-1c Gene Expression Is Negatively Regulated by Thyroid Hormone.
K. Hashimoto, M. Yamada, S. Matsumoto, T. Monden, T. Satoh, and M. Mori (2006)
Endocrinology 147, 4292-4302
   Abstract »    Full Text »    PDF »
Orphan nuclear receptors: therapeutic opportunities in skeletal muscle.
A. G. Smith and G. E. O. Muscat (2006)
Am J Physiol Cell Physiol 291, C203-C217
   Abstract »    Full Text »    PDF »
Retinoids Activate the RXR/SXR-Mediated Pathway and Induce the Endogenous CYP3A4 Activity in Huh7 Human Hepatoma Cells.
K. Wang, A. J. Mendy, G. Dai, H.-R. Luo, L. He, and Y.-J. Y. Wan (2006)
Toxicol. Sci. 92, 51-60
   Abstract »    Full Text »    PDF »
Reduced Fat Mass in Rats Fed a High Oleic Acid-Rich Safflower Oil Diet Is Associated with Changes in Expression of Hepatic PPAR{alpha} and Adipose SREBP-1c-Regulated Genes.
S.-C. Hsu and C.-j. Huang (2006)
J. Nutr. 136, 1779-1785
   Abstract »    Full Text »    PDF »
Transcriptional Regulation of Nephrin Gene by Peroxisome Proliferator-Activated Receptor-{gamma} Agonist: Molecular Mechanism of the Antiproteinuric Effect of Pioglitazone.
A. Benigni, C. Zoja, S. Tomasoni, M. Campana, D. Corna, C. Zanchi, E. Gagliardini, E. Garofano, D. Rottoli, T. Ito, et al. (2006)
J. Am. Soc. Nephrol. 17, 1624-1632
   Abstract »    Full Text »    PDF »
Decreased nuclear hormone receptor expression in the livers of mice in late pregnancy.
T. R. Sweeney, A. H. Moser, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold (2006)
Am J Physiol Endocrinol Metab 290, E1313-E1320
   Abstract »    Full Text »    PDF »
A Novel Pregnane X Receptor-mediated and Sterol Regulatory Element-binding Protein-independent Lipogenic Pathway.
J. Zhou, Y. Zhai, Y. Mu, H. Gong, H. Uppal, D. Toma, S. Ren, R. M. Evans, and W. Xie (2006)
J. Biol. Chem. 281, 15013-15020
   Abstract »    Full Text »    PDF »
Retinoic acid guides eye morphogenetic movements via paracrine signaling but is unnecessary for retinal dorsoventral patterning.
A. Molotkov, N. Molotkova, and G. Duester (2006)
Development 133, 1901-1910
   Abstract »    Full Text »    PDF »
Roles of Skeletal Muscle and Peroxisome Proliferator-Activated Receptors in the Development and Treatment of Obesity.
J. Lopez-Soriano, C. Chiellini, M. Maffei, P. A. Grimaldi, and J. M. Argiles (2006)
Endocr. Rev. 27, 318-329
   Abstract »    Full Text »    PDF »
Cutting Edge: Inhibition of the Retinoid X Receptor (RXR) Blocks T Helper 2 Differentiation and Prevents Allergic Lung Inflammation.
R. Grenningloh, A. Gho, P. di Lucia, M. Klaus, W. Bollag, I-C. Ho, F. Sinigaglia, and P. Panina-Bordignon (2006)
J. Immunol. 176, 5161-5166
   Abstract »    Full Text »    PDF »
The Lipoprotein Lipase Inhibitor ANGPTL3 Is Negatively Regulated by Thyroid Hormone.
C. Fugier, J.-J. Tousaint, X. Prieur, M. Plateroti, J. Samarut, and P. Delerive (2006)
J. Biol. Chem. 281, 11553-11559
   Abstract »    Full Text »    PDF »
Vitamin D Receptor Agonists Specifically Modulate the Volume of the Ligand-binding Pocket.
F. Molnar, M. Perakyla, and C. Carlberg (2006)
J. Biol. Chem. 281, 10516-10526
   Abstract »    Full Text »    PDF »
Differential Effects of Isoflavones, from Astragalus Membranaceus and Pueraria Thomsonii, on the Activation of PPAR{alpha}, PPAR{gamma}, and Adipocyte Differentiation In Vitro.
P. Shen, M. H. Liu, T. Y. Ng, Y. H. Chan, and E. L. Yong (2006)
J. Nutr. 136, 899-905
   Abstract »    Full Text »    PDF »
1,25-dihydroxyvitamin D3 and its receptor inhibit the chenodeoxycholic acid-dependent transactivation by farnesoid X receptor..
Y. Honjo, S. Sasaki, Y. Kobayashi, H. Misawa, and H. Nakamura (2006)
J. Endocrinol. 188, 635-643
   Abstract »    Full Text »    PDF »
Peroxisome Proliferator-Activated Receptors and Liver X Receptors in Atherosclerosis and Immunity.
G. D. Barish (2006)
J. Nutr. 136, 690-694
   Abstract »    Full Text »    PDF »
PPAR{delta} regulates glucose metabolism and insulin sensitivity.
C.-H. Lee, P. Olson, A. Hevener, I. Mehl, L.-W. Chong, J. M. Olefsky, F. J. Gonzalez, J. Ham, H. Kang, J. M. Peters, et al. (2006)
PNAS 103, 3444-3449
   Abstract »    Full Text »    PDF »
Peroxisome proliferator-activated receptor {delta} promotes very low-density lipoprotein-derived fatty acid catabolism in the macrophage.
C.-H. Lee, K. Kang, I. R. Mehl, R. Nofsinger, W. A. Alaynick, L.-W. Chong, J. M. Rosenfeld, and R. M. Evans (2006)
PNAS 103, 2434-2439
   Abstract »    Full Text »    PDF »
Cross-talk between Thyroid Hormone Receptor and Liver X Receptor Regulatory Pathways Is Revealed in a Thyroid Hormone Resistance Mouse Model.
K. Hashimoto, R. N. Cohen, M. Yamada, K. R. Markan, T. Monden, T. Satoh, M. Mori, and F. E. Wondisford (2006)
J. Biol. Chem. 281, 295-302
   Abstract »    Full Text »    PDF »
Liver X Receptor Activation and High-Density Lipoprotein Biology: A Reversal of Fortune?.
C.-H. Lee and J. Plutzky (2006)
Circulation 113, 5-8
   Full Text »    PDF »
NUCLEAR RECEPTOR EXPRESSION IN FETAL AND PEDIATRIC LIVER: CORRELATION WITH CYP3A EXPRESSION.
C. A. Vyhlidal, R. Gaedigk, and J. S. Leeder (2006)
Drug Metab. Dispos. 34, 131-137
   Abstract »    Full Text »    PDF »
Obesity, Peroxisome Proliferator-Activated Receptor, and Atherosclerosis in Type 2 Diabetes.
F. Blaschke, Y. Takata, E. Caglayan, R. E. Law, and W. A. Hsueh (2006)
Arterioscler. Thromb. Vasc. Biol. 26, 28-40
   Abstract »    Full Text »    PDF »
IGF-1 induces rat glomerular mesangial cells to accumulate triglyceride.
A. K. Berfield, A. Chait, J. F. Oram, R. A. Zager, A. C. Johnson, and C. K. Abrass (2006)
Am J Physiol Renal Physiol 290, F138-F147
   Abstract »    Full Text »    PDF »
Retinoid X Receptor Agonists Increase Bcl2a1 Expression and Decrease Apoptosis of Naive T Lymphocytes.
R. Rasooly, G. U. Schuster, J. P. Gregg, J.-H. Xiao, R. A. S. Chandraratna, and C. B. Stephensen (2005)
J. Immunol. 175, 7916-7929
   Abstract »    Full Text »    PDF »
Identification and characterization of two alternatively spliced transcript variants of human liver X receptor alpha.
M. Chen, S. Beaven, and P. Tontonoz (2005)
J. Lipid Res. 46, 2570-2579
   Abstract »    Full Text »    PDF »
T:G mismatch-specific thymine-DNA glycosylase (TDG) as a coregulator of transcription interacts with SRC1 family members through a novel tyrosine repeat motif.
M. J. Lucey, D. Chen, J. Lopez-Garcia, S. M. Hart, F. Phoenix, R. Al-Jehani, J. P. Alao, R. White, K. B. Kindle, R. Losson, et al. (2005)
Nucleic Acids Res. 33, 6393-6404
   Abstract »    Full Text »    PDF »
Downregulation of liver X receptor-{alpha} in mouse kidney and HK-2 proximal tubular cells by LPS and cytokines.
Y. Wang, A. H. Moser, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold (2005)
J. Lipid Res. 46, 2377-2387
   Abstract »    Full Text »    PDF »
Cytokine-dependent regulation of hepatic organic anion transporter gene transactivators in mouse liver.
A. Geier, C. G. Dietrich, S. Voigt, M. Ananthanarayanan, F. Lammert, A. Schmitz, M. Trauner, H. E. Wasmuth, D. Boraschi, N. Balasubramaniyan, et al. (2005)
Am J Physiol Gastrointest Liver Physiol 289, G831-G841
   Abstract »    Full Text »    PDF »
Transcriptional Repression of ATP-Binding Cassette Transporter A1 Gene in Macrophages: A Novel Atherosclerotic Effect of Angiotensin II.
Y. Takata, V. Chu, A. R. Collins, C. J. Lyon, W. Wang, F. Blaschke, D. Bruemmer, E. Caglayan, W. Daley, J. Higaki, et al. (2005)
Circ. Res. 97, e88-e96
   Abstract »    Full Text »    PDF »
A Nuclear Receptor Atlas: 3T3-L1 Adipogenesis.
M. Fu, T. Sun, A. L. Bookout, M. Downes, R. T. Yu, R. M. Evans, and D. J. Mangelsdorf (2005)
Mol. Endocrinol. 19, 2437-2450
   Abstract »    Full Text &r