Research Topics
Genomes and Genes
| David J MangelsdorfSummaryAffiliation: University of Texas Southwestern Medical Center Country: USA Publications
Research Grants
| Collaborators
|
Detail Information
Publications
Prevention of cholesterol gallstone disease by FXR agonists in a mouse modelAntonio Moschetta
Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390 9050, USA
Nat Med 10:1352-8. 2004..Taken together, these results indicate that FXR is a promising therapeutic target for treating or preventing cholesterol gallstone disease...
Commentary: the year in nuclear receptor control of metabolismDavid J Mangelsdorf
University of Texas Southwestern Medical Center, Howard Hughes Medical Institute, Department of Pharmacology, 6001 Forest Park Road, Room ND9 124A, Dallas, TX 75390 9050, USA
Mol Endocrinol 24:2075-80. 2010..These final selections were presented at "The Year In Basic Science Session" of the Annual Meeting of the Endocrine Society, ENDO 2010, the highlights of which are reproduced in this article...
FGF21 induces PGC-1alpha and regulates carbohydrate and fatty acid metabolism during the adaptive starvation responseMatthew J Potthoff
Department of Pharmacology, Howard Hughes Medical Institute, Advanced Imaging Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 106:10853-8. 2009..These results reveal an unexpected relationship between FGF21 and PGC-1alpha and demonstrate an important role for FGF21 in coordinately regulating carbohydrate and fatty acid metabolism during the progression from fasting to starvation...- FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1α pathwayMatthew J Potthoff
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9148, USA
Cell Metab 13:729-38. 2011..Overexpression of PGC-1α blocks the inhibitory effect of FGF15/19 on gluconeogenic gene expression. These results demonstrate that FGF15/19 works subsequent to insulin as a postprandial regulator of hepatic carbohydrate homeostasis... - Regulation of bile acid synthesis by fat-soluble vitamins A and DDaniel R Schmidt
Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9050, USA
J Biol Chem 285:14486-94. 2010..These results reveal an unexpected link between the intake of fat-soluble vitamins A and D and bile acid metabolism, which may have evolved as a means for these dietary vitamins to regulate their own absorption... - Liver receptor homolog-1 regulates bile acid homeostasis but is not essential for feedback regulation of bile acid synthesisYoun Kyoung Lee
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9041, USA
Mol Endocrinol 22:1345-56. 2008..Taken together, these data reveal a broad role for LRH-1 in regulating bile acid homeostasis but demonstrate that LRH-1 is either not involved in the feedback regulation of bile acid synthesis or is compensated for by other factors... - Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptorTakeshi Inagaki
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 103:3920-5. 2006.... - Liver LXRα expression is crucial for whole body cholesterol homeostasis and reverse cholesterol transport in miceYuan Zhang
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Clin Invest 122:1688-99. 2012..In sum, these observations suggest that therapeutic strategies that bypass the liver or limit the activation of hepatic LXRs should still be beneficial for the treatment of cardiovascular disease... - Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γWei Wei
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 109:3143-8. 2012..Therefore, FGF21 is a critical rheostat for bone turnover and a key integrator of bone and energy metabolism. These results reveal that skeletal fragility may be an undesirable consequence of chronic FGF21 administration... - Liver X receptors regulate adrenal cholesterol balanceCarolyn L Cummins
Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9050, USA
J Clin Invest 116:1902-12. 2006..These results imply LXRalpha provides a safety valve to limit free cholesterol levels as a basal protective mechanism in the adrenal gland, where cholesterol is under constant flux... - Identification of a hormonal basis for gallbladder fillingMihwa Choi
Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
Nat Med 12:1253-5. 2006..These studies demonstrate that gallbladder filling is actively regulated by an endocrine pathway and suggest a postprandial timing mechanism that controls gallbladder motility... - Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21Takeshi Inagaki
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Cell Metab 5:415-25. 2007..These findings demonstrate an unexpected role for the PPARalpha-FGF21 endocrine signaling pathway in regulating diverse metabolic and behavioral aspects of the adaptive response to starvation... - The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder fillingTingting Li
Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390 9050, USA
Mol Endocrinol 25:1066-71. 2011..They further suggest that TGR5 agonists should be assessed for effects on human gallbladder as they are developed for treating metabolic disease... - AKR1B7 is induced by the farnesoid X receptor and metabolizes bile acidsDaniel R Schmidt
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
J Biol Chem 286:2425-32. 2011..These findings reveal a feed-forward, protective pathway operative in murine enterohepatic tissues wherein FXR induces AKR1B7 to detoxify bile acids... - βKlotho is required for fibroblast growth factor 21 effects on growth and metabolismXunshan Ding
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Cell Metab 16:387-93. 2012..Taken together, these data demonstrate that βKlotho is essential for FGF21 activity and that βKlotho in adipose tissue contributes to the beneficial metabolic actions of FGF21... - A Nuclear Receptor Atlas: macrophage activationGrant D Barish
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, P.O. Box 85800, San Diego, California 92186-5800, USA
Mol Endocrinol 19:2466-77. 2005.... - A role for the apoptosis inhibitory factor AIM/Spalpha/Api6 in atherosclerosis developmentSatoko Arai
Center for Immunology, The University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard NA7200, Dallas, Texas 75390, USA
Cell Metab 1:201-13. 2005..We conclude that AIM production facilitates macrophage survival within atherosclerotic lesions and that loss of AIM decreases early lesion development by increasing macrophage apoptosis... - Identification of the nuclear receptor DAF-12 as a therapeutic target in parasitic nematodesZhu Wang
Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 106:9138-43. 2009..stercoralis DAF-12 ligand-binding domain cocrystallized with dafachronic acids. These results reveal the molecular basis for DAF-12 ligand binding and identify nuclear receptors as unique therapeutic targets in parasitic nematodes... - FXR agonists and FGF15 reduce fecal bile acid excretion in a mouse model of bile acid malabsorptionDiana Jung
Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9050, USA
J Lipid Res 48:2693-700. 2007..These findings suggest that FXR agonists or FGF15 could be used therapeutically to interrupt the cycle of excessive bile acid production in patients with bile acid malabsorption... - Sterol intermediates from cholesterol biosynthetic pathway as liver X receptor ligandsChendong Yang
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, 75390, USA
J Biol Chem 281:27816-26. 2006..These observations are consistent with specific intermediates in the cholesterol biosynthetic pathway regulating lipid homeostasis through both the LXR and sterol response element-binding protein pathways... - Liver X receptor-dependent repression of matrix metalloproteinase-9 expression in macrophagesAntonio Castrillo
Howard Hughes Medical Institute, University of California, Los Angeles 90095, USA
J Biol Chem 278:10443-9. 2003..These observations identify the regulation of macrophage MMP-9 expression as a mechanism whereby activation of LXRs may impact macrophage inflammatory responses... - Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasisTakeshi Inagaki
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Cell Metab 2:217-25. 2005..These studies define FGF15 and FGFR4 as components of a gut-liver signaling pathway that synergizes with SHP to regulate bile acid synthesis... - FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesisSerkan Kir
Department of Pharmacology, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, TX 75390, USA
Science 331:1621-4. 2011..FGF19 treatment restored the loss of glycogen in diabetic animals lacking insulin. Thus, FGF19 activates a physiologically important, insulin-independent endocrine pathway that regulates hepatic protein and glycogen metabolism... - Inhibition of growth hormone signaling by the fasting-induced hormone FGF21Takeshi Inagaki
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Cell Metab 8:77-83. 2008..Chronic exposure to FGF21 markedly inhibits growth in mice. These data suggest a central role for FGF21 in inhibiting growth as part of its broader role in inducing the adaptive response to starvation... - Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouseKlementina Fon Tacer
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Mol Endocrinol 24:2050-64. 2010..This FGF atlas provides an important resource for guiding future studies to elucidate the physiological functions of FGFs in adult animals... - Structural determinants of allosteric ligand activation in RXR heterodimersAndrew I Shulman
Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
Cell 116:417-29. 2004..These results reveal a structural network required for RXR heterodimer allosteric communication and suggest that the specificity of ligand response and permissivity coevolved to enable signal discrimination... - Fibroblast growth factor-21 regulates PPARγ activity and the antidiabetic actions of thiazolidinedionesPaul A Dutchak
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9041, USA
Cell 148:556-67. 2012..Adding back FGF21 prevents sumoylation and restores PPARγ activity. Collectively, these results reveal FGF21 as a key mediator of the physiologic and pharmacologic actions of PPARγ... - 27-Hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogenMichihisa Umetani
Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, Texas 75390 9050, USA
Nat Med 13:1185-92. 2007..Taken together, these studies point to 27HC as a contributing factor in the loss of estrogen protection from vascular disease... - Fibroblast growth factor 21: from pharmacology to physiologySteven A Kliewer
Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 73590 9041, USA
Am J Clin Nutr 91:254S-257S. 2010..This article highlights recent advances in our understanding of FGF21's pharmacologic and physiologic actions... - Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional networkAngie L Bookout
Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 6001 Forest Park Road, Dallas, 75390, USA
Cell 126:789-99. 2006..These data reveal a hierarchical transcriptional circuitry that extends beyond individual tissues to form a meganetwork governing physiology on an organismal scale... - Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretionLiqing Yu
McDermott Center for Human Growth and Development, Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9046, USA
J Biol Chem 280:8742-7. 2005..Thus G5 and G8 are required to modulate biliary cholesterol secretion in response to cholate and diosgenin, but the choleretic effects of these two steroids are mediated by different mechanisms requiring FXR and PXR, respectively... - LXRs regulate the balance between fat storage and oxidationNada Y Kalaany
Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390, USA
Cell Metab 1:231-44. 2005..These studies suggest that, by selectively sensing the cholesterol component of a lipid-rich diet, LXRs govern the balance between storage and oxidation of dietary fat... - LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive functionSam R Holmstrom
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
Genes Dev 25:1674-9. 2011..Thus, LRH-1 is a key regulator of the exocrine pancreas-specific transcriptional network required for the production and secretion of pancreatic fluid... - MicroRNA let-7 regulates 3T3-L1 adipogenesisTingwan Sun
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, 75390 9050, USA
Mol Endocrinol 23:925-31. 2009..These results suggest that let-7 plays an important role in adipocyte differentiation and that it does so in part by targeting HMGA2, thereby regulating the transition from clonal expansion to terminal differentiation... - Nuclear receptors of the enteric tract: guarding the frontierDaniel R Schmidt
The Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas 75390 9050, USA
Nutr Rev 66:S88-97. 2008..The major homeostatic functions of the enteric nuclear receptor network are the topic of this review... - Synthesis and activity of dafachronic acid ligands for the C. elegans DAF-12 nuclear hormone receptorKamalesh K Sharma
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Mol Endocrinol 23:640-8. 2009..Potency derives more from the A/B-ring configuration than from the stereochemistry at C-25... - Enzymatic reduction of oxysterols impairs LXR signaling in cultured cells and the livers of miceWenling Chen
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Cell Metab 5:73-9. 2007..We conclude that oxysterols are in vivo ligands for LXR... - LuXuRies of lipid homeostasis: the unity of nuclear hormone receptors, transcription regulation, and cholesterol sensingYuan Zhang
Department of Pharmacology, Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9050, USA
Mol Interv 2:78-87. 2002..These findings define LXRs as potential therapeutic targets for the treatment of lipid disorders... - The starvation hormone, fibroblast growth factor-21, extends lifespan in miceYuan Zhang
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, United States
elife 1:e00065. 2012..These findings raise the possibility that FGF21 can be used to extend lifespan in other species.DOI:http://dx.doi.org/10.7554/eLife.00065.001... - Sterol-dependent nuclear import of ORP1S promotes LXR regulated trans-activation of apoESungsoo Lee
Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390 9039, United States
Exp Cell Res 318:2128-42. 2012..1 and ME.2 enhancer elements of the apoE gene. We propose that ORP1S is a cytoplasmic sterol sensor, which transports sterols to the nucleus and promotes LXR-dependent gene transcription through select enhancer elements... - Endocrine fibroblast growth factors 15/19 and 21: from feast to famineMatthew J Potthoff
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, 75390, USA
Genes Dev 26:312-24. 2012..FGF21 also acts in an autocrine fashion in several tissues, including adipose. The pharmacological actions of FGF15/19 and FGF21 make them attractive drug candidates for treating metabolic disease... - Partial resistance to peroxisome proliferator-activated receptor-alpha agonists in ZDF rats is associated with defective hepatic mitochondrial metabolismSanthosh Satapati
The Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Diabetes 57:2012-21. 2008..The purpose of this study is to determine whether abnormal mitochondrial metabolism plays a role in the dysregulation of both hepatic fat and glucose metabolism during diabetes... - Identification of ligands for DAF-12 that govern dauer formation and reproduction in C. elegansDaniel L Motola
Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA
Cell 124:1209-23. 2006.... - Retinoid x receptor heterodimers in the metabolic syndromeAndrew I Shulman
Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75390, USA
N Engl J Med 353:604-15. 2005 - Expression of LRH-1 and SF-1 in the mouse ovary: localization in different cell types correlates with differing functionMargaret M Hinshelwood
Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390 9038, USA
Mol Cell Endocrinol 207:39-45. 2003..Based on these findings, we propose that LRH-1 plays an important role as a competence factor in regulating aromatase, and thus estrogen biosynthesis, in ovary... - The Drosophila orphan nuclear receptor DHR38 mediates an atypical ecdysteroid signaling pathwayKeith D Baker
Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
Cell 113:731-42. 2003..Taken together, these data reveal the existence of a separate structural class of nuclear receptors that is conserved from fly to humans... - A Nuclear Receptor Atlas: 3T3-L1 adipogenesisMingui Fu
Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 6001 Forest Park Road, Dallas, Texas 75390-9050, USA
Mol Endocrinol 19:2437-50. 2005.... - Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylaseJeffrey B Cheng
Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
Proc Natl Acad Sci U S A 101:7711-5. 2004..These data identify CYP2R1 as a biologically relevant vitamin D 25-hydroxylase and reveal the molecular basis of a human genetic disease, selective 25-hydroxyvitamin D deficiency... - Identification of a liver-specific uridine phosphorylase that is regulated by multiple lipid-sensing nuclear receptorsYuan Zhang
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9050, USA
Mol Endocrinol 18:851-62. 2004.... - Nuclear receptor regulation of stemness and stem cell differentiationYangsik Jeong
Department of Pharmacology and Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Texas 75390, USA
Exp Mol Med 41:525-37. 2009..These studies provide insights into the therapeutic potential of the NR superfamily in stem cell therapy and in treating stem cell-associated diseases (e.g., cancer stem cell)... - High-throughput real-time quantitative reverse transcription PCRAngie L Bookout
Howard Hughes Medical Institute, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Curr Protoc Mol Biol . 2006..This protocol describes the production and quantitation of synthetic RNA molecules for real-time and non-real-time RT-PCR applications... - Liver X receptor signaling pathways in cardiovascular diseasePeter Tontonoz
Howard Hughes Medical Institute, University of California, Los Angeles School of Medicine, Box 951662, Los Angeles, California 90095 1662, USA
Mol Endocrinol 17:985-93. 2003..These observations identify the LXR pathway as a potential target for therapeutic intervention in human cardiovascular disease... - The liver X receptor gene team: potential new players in atherosclerosisJoyce J Repa
Department of Physiology, Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, Texas, USA
Nat Med 8:1243-8. 2002 - Nuclear receptor expression defines a set of prognostic biomarkers for lung cancerYangsik Jeong
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, United States of America
PLoS Med 7:e1000378. 2010.... - Reciprocal regulation of inflammation and lipid metabolism by liver X receptorsSean B Joseph
Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, California, USA
Nat Med 9:213-9. 2003..These findings identify LXRs as lipid-dependent regulators of inflammatory gene expression that may serve to link lipid metabolism and immune functions in macrophages... - De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilaseJeffrey B Cheng
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75390, USA
J Biol Chem 278:38084-93. 2003..CYP2R1 mRNA is abundant in the liver and testis, and present at lower levels in other tissues. The data suggest that CYP2R1 is a strong candidate for the microsomal vitamin D 25-hydroxylase... - Vitamin D receptor as an intestinal bile acid sensorMakoto Makishima
Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390 9050, USA
Science 296:1313-6. 2002..These studies offer a mechanism that may explain the proposed protective effects of vitamin D and its receptor against colon cancer...
Research Grants
- Conference on Nuclear Receptor SuperfamilyDavid Mangelsdorf; Fiscal Year: 2002....
- Nuclear Receptors: Orphan BrothersDavid Mangelsdorf; Fiscal Year: 2004....
- MECHANISMS OF DRUG ACTION AND DISPOSITIONDavid Mangelsdorf; Fiscal Year: 2007..This program seeks to train the next generation of scientists who will make these discoveries and insure that scientific research on human health remains vibrant and at the cutting edge. ..