bile acids and salts

Summary

Summary: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones.

Top Publications

  1. ncbi Identification of a nuclear receptor for bile acids
    M Makishima
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 9050, USA
    Science 284:1362-5. 1999
  2. ncbi Bile salt biotransformations by human intestinal bacteria
    Jason M Ridlon
    Department of Microbiology Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA
    J Lipid Res 47:241-59. 2006
  3. ncbi Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
    Mitsuhiro Watanabe
    Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS INSERM ULP, 1 rue Laurent Fries, 67404 Illkirch, France
    Nature 439:484-9. 2006
  4. ncbi Targeting bile-acid signalling for metabolic diseases
    Charles Thomas
    Institute of Genetics and Molecular and Cellular Biology, 1 rue Laurent Fries, 67404 Illkirch, France
    Nat Rev Drug Discov 7:678-93. 2008
  5. pmc Xenobiotic, bile acid, and cholesterol transporters: function and regulation
    Curtis D Klaassen
    Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160 7417, USA
    Pharmacol Rev 62:1-96. 2010
  6. pmc TGR5-mediated bile acid sensing controls glucose homeostasis
    Charles Thomas
    Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS INSERM ULP, 67404 Illkirch, France
    Cell Metab 10:167-77. 2009
  7. ncbi Bile acids: natural ligands for an orphan nuclear receptor
    D J Parks
    Department of Molecular Biochemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA
    Science 284:1365-8. 1999
  8. ncbi Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha
    D J Peet
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 75235 9050, USA
    Cell 93:693-704. 1998
  9. ncbi Role of bile acids and bile acid receptors in metabolic regulation
    Philippe Lefebvre
    Institut National de la Sante et de la Recherche Medicale, Lille, France
    Physiol Rev 89:147-91. 2009
  10. ncbi Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
    Takeshi Inagaki
    Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Cell Metab 2:217-25. 2005

Detail Information

Publications338 found, 100 shown here

  1. ncbi Identification of a nuclear receptor for bile acids
    M Makishima
    Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235 9050, USA
    Science 284:1362-5. 1999
    ..These results demonstrate a mechanism by which bile acids transcriptionally regulate their biosynthesis and enterohepatic transport...
  2. ncbi Bile salt biotransformations by human intestinal bacteria
    Jason M Ridlon
    Department of Microbiology Immunology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA
    J Lipid Res 47:241-59. 2006
    ....
  3. ncbi Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation
    Mitsuhiro Watanabe
    Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS INSERM ULP, 1 rue Laurent Fries, 67404 Illkirch, France
    Nature 439:484-9. 2006
    ..The BA-TGR5-cAMP-D2 signalling pathway is therefore a crucial mechanism for fine-tuning energy homeostasis that can be targeted to improve metabolic control...
  4. ncbi Targeting bile-acid signalling for metabolic diseases
    Charles Thomas
    Institute of Genetics and Molecular and Cellular Biology, 1 rue Laurent Fries, 67404 Illkirch, France
    Nat Rev Drug Discov 7:678-93. 2008
    ....
  5. pmc Xenobiotic, bile acid, and cholesterol transporters: function and regulation
    Curtis D Klaassen
    Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160 7417, USA
    Pharmacol Rev 62:1-96. 2010
    ..Transporters are important transmembrane proteins that mediate the cellular entry and exit of a wide range of substrates throughout the body and thereby play important roles in human physiology, pharmacology, pathology, and toxicology...
  6. pmc TGR5-mediated bile acid sensing controls glucose homeostasis
    Charles Thomas
    Institut de Génétique et Biologie Moléculaire et Cellulaire, CNRS INSERM ULP, 67404 Illkirch, France
    Cell Metab 10:167-77. 2009
    ....
  7. ncbi Bile acids: natural ligands for an orphan nuclear receptor
    D J Parks
    Department of Molecular Biochemistry, Glaxo Wellcome Research and Development, Research Triangle Park NC, 27709, USA
    Science 284:1365-8. 1999
    ..These results provide evidence for a nuclear bile acid signaling pathway that may regulate cholesterol homeostasis...
  8. ncbi Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha
    D J Peet
    Howard Hughes Medical Institute, Department of Pharmacology, University of Texas Southwestern Medical Center at Dallas, 75235 9050, USA
    Cell 93:693-704. 1998
    ..These results demonstrate the existence of a physiologically significant feed-forward regulatory pathway for sterol metabolism and establish the role of LXR alpha as the major sensor of dietary cholesterol...
  9. ncbi Role of bile acids and bile acid receptors in metabolic regulation
    Philippe Lefebvre
    Institut National de la Sante et de la Recherche Medicale, Lille, France
    Physiol Rev 89:147-91. 2009
    ..Taken together, these findings suggest that modulation of FXR activity and BA metabolism may open new attractive pharmacological approaches for the treatment of the metabolic syndrome and type 2 diabetes...
  10. ncbi Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis
    Takeshi 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...
  11. pmc Bile salts and glycine as cogerminants for Clostridium difficile spores
    Joseph A Sorg
    Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Bacteriol 190:2505-12. 2008
    ..difficile spores but prevented the growth of vegetative C. difficile. A model of resistance to C. difficile colonization mediated by the normal bacterial flora is proposed...
  12. pmc Bile acids: regulation of synthesis
    John Y L Chiang
    Department of Integrative Medical Sciences, Northeastern Ohio University s Colleges of Medicine and Pharmacy, Rootstown, OH 44272, USA
    J Lipid Res 50:1955-66. 2009
    ..Bile acids and bile acid receptors are therapeutic targets for development of drugs for treatment of cholestatic liver diseases, fatty liver diseases, diabetes, obesity, and metabolic syndrome...
  13. ncbi Targeted disruption of the nuclear receptor FXR/BAR impairs bile acid and lipid homeostasis
    C J Sinal
    Laboratory of Metabolism, Division of Basic Sciences, National Institutes of Health, Bethesda, Maryland 20892, USA
    Cell 102:731-44. 2000
    ..These data demonstrate that FXR/BAR is critical for bile acid and lipid homeostasis by virtue of its role as an intracellular bile acid sensor...
  14. ncbi A regulatory cascade of the nuclear receptors FXR, SHP-1, and LRH-1 represses bile acid biosynthesis
    B Goodwin
    Department of Molecular Endocrinology, Glaxo Wellcome Research and Development, Research Triangle Park, North Carolina 27709, USA
    Mol Cell 6:517-26. 2000
    ..This bile acid-activated regulatory cascade provides a molecular basis for the coordinate suppression of CYP7A1 and other genes involved in bile acid biosynthesis...
  15. ncbi The interaction between bacteria and bile
    Maire Begley
    Department of Microbiology and Alimentary Pharmabiotic Centre, University College Cork, Ireland
    FEMS Microbiol Rev 29:625-51. 2005
    ..The molecular mechanisms underlying bile tolerance are investigated and the relationship between bile and virulence is examined. Finally, the potential benefits of bile research are briefly discussed...
  16. pmc Bile acids as regulatory molecules
    Phillip B Hylemon
    Department of Microbiology and Immunology, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298 0678, USA
    J Lipid Res 50:1509-20. 2009
    ..In this review, we will summarize the current knowledge of how bile acids regulate hepatic lipid and glucose metabolism through the activation of specific nuclear receptors and cell signaling pathways...
  17. pmc Systemic gut microbial modulation of bile acid metabolism in host tissue compartments
    Jonathan R Swann
    Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College, London SW7 2AZ, United Kingdom
    Proc Natl Acad Sci U S A 108:4523-30. 2011
    ....
  18. ncbi Identification of membrane-type receptor for bile acids (M-BAR)
    Takaharu Maruyama
    Tsukuba Research Institute, Banyu Pharmaceutical Co, Ltd, Okubo 3, Tsukuba, Ibaraki, Japan
    Biochem Biophys Res Commun 298:714-9. 2002
    ..Expression of BG37 was detected in various specific tissues, suggesting its physiological role, although it remains to be further characterized...
  19. pmc Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor
    Takeshi 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
    ....
  20. ncbi The sister of P-glycoprotein represents the canalicular bile salt export pump of mammalian liver
    T Gerloff
    Division of Clinical Pharmacology and Toxicology, Department of Medicine, University Hospital, CH 8091 Zurich, Switzerland
    J Biol Chem 273:10046-50. 1998
    ..These results indicate that the sister of P-glycoprotein is the major canalicular bile salt export pump of mammalian liver...
  21. pmc Crystal structure of a bacterial homologue of the bile acid sodium symporter ASBT
    Nien Jen Hu
    Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, UK
    Nature 478:408-11. 2011
    ..The position of the taurocholate molecule, together with the molecular architecture, suggests the rudiments of a possible transport mechanism...
  22. pmc Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis
    Jason A Holt
    Nuclear Receptor Discovery Research, High Throughput Biology, Gene Interference, Transgenics, GlaxoSmithKline, Research Triangle Park, North Carolina 27709, USA
    Genes Dev 17:1581-91. 2003
    ..This signaling cascade defines a novel mechanism for feedback repression of bile acid biosynthesis and underscores the vital role of FXR in the regulation of multiple pathways of cholesterol catabolism in the liver...
  23. pmc Active efflux of bile salts by Escherichia coli
    D G Thanassi
    Department of Molecular and Cell Biology, University of California, Berkeley 94720 3206, USA
    J Bacteriol 179:2512-8. 1997
    ..It followed saturation kinetics with Vmax and Km values in the neighborhood of 0.3 nmol min(-1) mg of protein(-1) and 50 microM, respectively...
  24. ncbi Redundant pathways for negative feedback regulation of bile acid production
    Li Wang
    Department of Molecular and Cellular Biology, Houston, TX 77030, USA
    Dev Cell 2:721-31. 2002
    ..We provide evidence for two such pathways, based on activation of the xenobiotic receptor PXR or the c-Jun N-terminal kinase JNK. We conclude that redundant mechanisms regulate this critical aspect of cholesterol homeostasis...
  25. ncbi A G protein-coupled receptor responsive to bile acids
    Yuji Kawamata
    Discovery Research Laboratories 1, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd, Wadai 10, Tsukuba, Ibaraki 300 4293, Japan
    J Biol Chem 278:9435-40. 2003
    ....
  26. ncbi The enzymes, regulation, and genetics of bile acid synthesis
    David W Russell
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390 9046, USA
    Annu Rev Biochem 72:137-74. 2003
    ..Inherited mutations that impair bile acid synthesis cause a spectrum of human disease; this ranges from liver failure in early childhood to progressive neuropathy in adults...
  27. pmc Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities
    Rohit Kohli
    Cincinnati Children s Hospital Medical Center, Department of Pediatrics, University of Cincinnati College of Medicine, Ohio, USA
    Am J Physiol Gastrointest Liver Physiol 299:G652-60. 2010
    ..Changes in serum bile acids or bile acid enterohepatic recycling may mediate the metabolic benefits seen after bariatric surgery...
  28. pmc Inhibiting the initiation of Clostridium difficile spore germination using analogs of chenodeoxycholic acid, a bile acid
    Joseph A Sorg
    Department of Molecular Biology and Microbiology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA 02111, USA
    J Bacteriol 192:4983-90. 2010
    ..Some of these compounds resist 7α-dehydroxylation by Clostridium scindens, a core member of the normal human colonic microbiota, suggesting that they are more stable than chenodeoxycholate in the colonic environment...
  29. pmc Trade-off between bile resistance and nutritional competence drives Escherichia coli diversification in the mouse gut
    Marianne De Paepe
    INSERM, U989, Universite Paris Descartes, Paris, France
    PLoS Genet 7:e1002107. 2011
    ..These results illustrate how experimental evolution in natural environments enables identification of both the selective pressures that organisms face in their natural environment and the diversification mechanisms...
  30. pmc Glucose and insulin induction of bile acid synthesis: mechanisms and implication in diabetes and obesity
    Tiangang Li
    Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio 44272, USA
    J Biol Chem 287:1861-73. 2012
    ..Glucose induces CYP7A1 gene expression mainly by epigenetic mechanisms. In diabetic mice, CYP7A1 chromatin is hyperacetylated, and fasting to refeeding response is impaired and may exacerbate metabolic disorders in diabetes...
  31. ncbi The continuing importance of bile acids in liver and intestinal disease
    A F Hofmann
    Department of Medicine, University of California, San Diego, La Jolla 92093 0813, USA
    Arch Intern Med 159:2647-58. 1999
    ..A knowledge of bile acid physiology and the perturbations of bile acid metabolism in liver and digestive disease should be useful for the internist...
  32. ncbi Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration
    Wendong Huang
    Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Science 312:233-6. 2006
    ..FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth...
  33. ncbi A gene encoding a liver-specific ABC transporter is mutated in progressive familial intrahepatic cholestasis
    S S Strautnieks
    Department of Paediatrics, University College London Medical School, UK
    Nat Genet 20:233-8. 1998
    ..The product of the orthologous rat gene has been shown to be an effective bile acid transporter in vitro. These data provide evidence that SPGP is the human bile salt export pump (BSEP)...
  34. ncbi Role of nuclear receptors in the adaptive response to bile acids and cholestasis: pathogenetic and therapeutic considerations
    Gernot Zollner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Austria, and Karolinska University Hospital Huddinge, Stockholm, Sweden
    Mol Pharm 3:231-51. 2006
    ..Therefore, additional therapeutic strategies such as targeted activation of nuclear receptors are needed to enhance the hepatic defense against toxic bile acids...
  35. ncbi Elevated cholesterol metabolism and bile acid synthesis in mice lacking membrane tyrosine kinase receptor FGFR4
    C Yu
    Department of Biochemistry and Biophysics, Texas A and M University, Institute of Biosciences and Technology, Texas A and M University System Health Science Center, Houston, Texas 77030 3303, USA
    J Biol Chem 275:15482-9. 2000
    ....
  36. pmc Bile-acid-induced cell injury and protection
    Maria J Perez
    Department of Biochemistry and Molecular Biology Campus Miguel de Unamuno E D 129, Salamanca, Spain
    World J Gastroenterol 15:1677-89. 2009
    ..Other natural BAs or their derivatives, such as cholyl-N-methylglycine or cholylsarcosine, have also aroused pharmacological interest owing to their protective properties...
  37. ncbi Nuclear receptors in liver disease
    Martin Wagner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Austria
    Hepatology 53:1023-34. 2011
    ....
  38. ncbi Prevention of cholesterol gallstone disease by FXR agonists in a mouse model
    Antonio 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...
  39. ncbi Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism
    Mary Elizabeth Patti
    Harvard Medical School, Harvard University, Boston, Massachusetts, USA
    Obesity (Silver Spring) 17:1671-7. 2009
    ..57, P = 0.004). Together, our data suggest that altered bile acid levels and composition may contribute to improved glucose and lipid metabolism in patients who have had GB...
  40. ncbi Circulating intestinal fibroblast growth factor 19 has a pronounced diurnal variation and modulates hepatic bile acid synthesis in man
    T Lundåsen
    Metabolism Unit, Department of Endocrinology, Metabolism and Diabetes, Center for Nutrition and Toxicology, Karolinska Institute, Karolinska University Hospital Huddinge, Stockholm, Sweden
    J Intern Med 260:530-6. 2006
    ..Through its systemic effects, circulating FGF19 may also mediate other known BA-dependent effects on lipid and carbohydrate metabolism...
  41. pmc Human cholesterol 7alpha-hydroxylase (CYP7A1) deficiency has a hypercholesterolemic phenotype
    Clive R Pullinger
    Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA 94143 0130, USA
    J Clin Invest 110:109-17. 2002
    ..Study of the kindred, which is of English and Celtic background, revealed that individuals heterozygous for the mutation are also hyperlipidemic, indicating that this is a codominant disorder...
  42. ncbi Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates
    Anna Glantz
    Department of Obstetrics and Gynaecology, Sahlgrenska University Hospital East, Goteborg, Sweden
    Hepatology 40:467-74. 2004
    ..No increase in fetal risk was detected in ICP patients with bile acid levels < 40 micromol/L, and we propose that these women be managed expectantly, which would significantly reduce the costs of medical care...
  43. ncbi Bile acids: chemistry, pathochemistry, biology, pathobiology, and therapeutics
    A F Hofmann
    Department of Medicine, University of California, San Diego, La Jolla, California 92093 0063, USA
    Cell Mol Life Sci 65:2461-83. 2008
    ..Bile acids are used therapeutically to correct deficiency states, to decrease the cholesterol saturation of bile, or to decrease the cytotoxicity of retained bile acids in cholestatic liver disease...
  44. ncbi CAR and PXR agonists stimulate hepatic bile acid and bilirubin detoxification and elimination pathways in mice
    Martin Wagner
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Medicine, Medical University Graz, Auenbruggerplatz 15, A 8036 Graz, Austria
    Hepatology 42:420-30. 2005
    ....
  45. ncbi Bile acids as regulators of hepatic lipid and glucose metabolism
    Michael Trauner
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
    Dig Dis 28:220-4. 2010
    ..Collectively, these findings suggest that BA and targeting their receptor/signaling pathways may represent a promising approach to treat NAFLD and closely linked disorders such as obesity, diabetes, dyslipidemia and arteriosclerosis...
  46. pmc Dual farnesoid X receptor/TGR5 agonist INT-767 reduces liver injury in the Mdr2-/- (Abcb4-/-) mouse cholangiopathy model by promoting biliary HCO⁻₃ output
    Anna Baghdasaryan
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
    Hepatology 54:1303-12. 2011
    ..In addition, INT-767 dramatically reduced bile acid synthesis via the induction of ileal Fgf15 and hepatic Shp gene expression, thus resulting in significantly reduced biliary bile acid output in Mdr2(-/-) mice...
  47. pmc The G protein-coupled bile acid receptor, TGR5, stimulates gallbladder filling
    Tingting 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...
  48. pmc Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol
    Liqing Yu
    Department of Molecular Genetics and McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390 9046, USA
    J Clin Invest 110:671-80. 2002
    ....
  49. ncbi FXR, a multipurpose nuclear receptor
    Florence Y Lee
    Department of Biological Chemistry, University of California at Los Angeles, Los Angeles, CA 90095, USA
    Trends Biochem Sci 31:572-80. 2006
    ..Thus, the development of FXR agonists might prove useful for the treatment of diabetes, cholesterol gallstones, and hepatic and intestinal toxicity...
  50. ncbi Effect of bile salts on the DNA and membrane integrity of enteric bacteria
    Megan E Merritt
    Department of Biological Sciences, Mississippi State University, Box GY, Mississippi State, MS 39762, USA
    J Med Microbiol 58:1533-41. 2009
    ..We discuss the findings from recent investigations that indicate bile tolerance is dependent upon being able to resist the detergent properties of bile at both the membrane and DNA level...
  51. pmc Bile acid transporters
    Paul A Dawson
    Department of Internal Medicine and Department of Pathology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    J Lipid Res 50:2340-57. 2009
    ..This article will review our current understanding of the physiological role and regulation of these important carriers...
  52. ncbi Nuclear receptors and lipid physiology: opening the X-files
    A Chawla
    Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, Post Office Box 85800, San Diego, CA 92186 5800, USA
    Science 294:1866-70. 2001
    ....
  53. pmc Loss of nuclear receptor SHP impairs but does not eliminate negative feedback regulation of bile acid synthesis
    Thomas A Kerr
    Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75390, USA
    Dev Cell 2:713-20. 2002
    ..We conclude that input from three negative regulatory pathways controls bile acid synthesis. One is mediated by SHP, and two are SHP independent and invoked by liver damage and changes in bile acid pool size...
  54. ncbi Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor
    M Ananthanarayanan
    Laboratory of Developmental and Molecular Hepatology, Department of Pediatrics, The Mount Sinai Medical Center, New York, New York 10029, USA
    J Biol Chem 276:28857-65. 2001
    ..These results demonstrate a mechanism by which bile acids transcriptionally regulate the activity of the bile salt excretory pump, a critical component involved in the enterohepatic circulation of bile acids...
  55. ncbi Expression and function of the bile acid receptor TGR5 in Kupffer cells
    Verena Keitel
    Clinic for Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Moorenstrasse 5, D 40225 Dusseldorf, Germany
    Biochem Biophys Res Commun 372:78-84. 2008
    ....
  56. ncbi Bile salt transporters: molecular characterization, function, and regulation
    Michael Trauner
    Division of Gastroenterology and Hepatology, Department of Internal Medicine, Karl Franzens University, School of Medicine, Graz, Austria
    Physiol Rev 83:633-71. 2003
    ..This review is a comprehensive summary of current knowledge of the molecular characterization, function, and regulation of bile salt transporters in normal physiology and in cholestatic liver disease and liver regeneration...
  57. pmc Compromised intestinal lipid absorption in mice with a liver-specific deficiency of liver receptor homolog 1
    Chikage Mataki
    Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS INSERM ULP, 67404 Illkirch, France
    Mol Cell Biol 27:8330-9. 2007
    ..Our studies unequivocally demonstrate a pivotal role for LRH-1 in determining the composition of BAs, which, in turn has major consequences on whole-body lipid homeostasis...
  58. ncbi Tauroursodeoxycholic acid protects rat hepatocytes from bile acid-induced apoptosis via activation of survival pathways
    Marieke H Schoemaker
    Center for Liver, Digestive and Metabolic Diseases, Groningen University Institute for Drug Exploration, Groningen, The Netherlands
    Hepatology 39:1563-73. 2004
    ..In conclusion, TUDCA contributes to the protection against GCDCA-induced mitochondria-controlled apoptosis by activating survival pathways...
  59. pmc Relevant use of Klotho in FGF19 subfamily signaling system in vivo
    Ken ichi Tomiyama
    Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 107:1666-71. 2010
    ..One-to-one functional interactions such as alpha-Klotho/FGF23, beta-Klotho/FGF15 (humanFGF19), and undefined cofactor/FGF21 would result in tissue-specific signal transduction of the FGF19 subfamily...
  60. ncbi Bile-acid-activated receptors: targeting TGR5 and farnesoid-X-receptor in lipid and glucose disorders
    Stefano Fiorucci
    Dipartimento di Medicina Clinica e Sperimentale, Universita degli Studi di Perugia, Perugia, Italy
    Trends Pharmacol Sci 30:570-80. 2009
    ..The development of dual FXR and TGR5 ligands could provide new opportunities for the treatment of lipid and glucose disorders...
  61. ncbi Colesevelam improves insulin resistance in a diet-induced obesity (F-DIO) rat model by increasing the release of GLP-1
    Quan Shang
    Department of Medicine, University of Medicine and Dentistry of New Jersey, Newark, USA
    Am J Physiol Gastrointest Liver Physiol 298:G419-24. 2010
    ..It is unlikely that the improvement is attributable to decreased bile acid flux to the liver but is likely secondary to induced GLP-1 secretion, which improves insulin release...
  62. ncbi Nuclear bile acid receptor FXR protects against intestinal tumorigenesis
    Salvatore Modica
    Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa MariaImbaro, Chieti and Clinica Medica A Murri, University of Bari, Bari, Italy
    Cancer Res 68:9589-94. 2008
    ..Thus, from a therapeutic standpoint, strategies aimed at reactivating FXR expression in colon tumors might be useful in treatment of colon cancer...
  63. pmc A bile acid-like steroid modulates Caenorhabditis elegans lifespan through nuclear receptor signaling
    Birgit Gerisch
    Max Planck Institut fuer Molekulare Genetik, Ihnestrasse 73, 14195 Berlin, Germany
    Proc Natl Acad Sci U S A 104:5014-9. 2007
    ..Thus, dafachronic acid regulates C. elegans lifespan according to signaling state. These studies provide key evidence that bile acid-like steroids modulate aging in animals...
  64. pmc The thyroid hormone mimetic compound KB2115 lowers plasma LDL cholesterol and stimulates bile acid synthesis without cardiac effects in humans
    Anders Berkenstam
    Karo Bio AB, Novum Research Park, S 141 57 Huddinge, Sweden
    Proc Natl Acad Sci U S A 105:663-7. 2008
    ..Thus, selective thyromimetics deserve further study as agents to treat dyslipidemia and other risk factors for atherosclerosis...
  65. pmc Metabolism of bile salts in mice influences spore germination in Clostridium difficile
    Jennifer L Giel
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America
    PLoS ONE 5:e8740. 2010
    ..Taken together, these data suggest that an in vivo-produced compound, likely bile salts, stimulates colony formation from C. difficile spores and that levels of this compound are influenced by the commensal gastrointestinal flora...
  66. ncbi Changes of organic anion transporter MRP4 and related nuclear receptors in human obstructive cholestasis
    Jin Chai
    Institute of Gastroenterology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, People s Republic of China
    J Gastrointest Surg 15:996-1004. 2011
    ..We collected liver samples from patients with obstructive cholestasis or without liver disease and investigated the expression of MRP4 and NRs CAR, PXR, and RXRα by semi-quantitative RT-PCR, Western blot and immunostaining assays...
  67. pmc Farnesoid X receptor deficiency improves glucose homeostasis in mouse models of obesity
    Janne Prawitt
    University of Lille Nord de France, Inserm UMR1011, UDSL, Institut Pasteur de Lille, Lille, France
    Diabetes 60:1861-71. 2011
    ..However, the role of FXR in obesity and associated complications, such as dyslipidemia and insulin resistance, has not been directly assessed...
  68. ncbi Vitamin D receptor-dependent regulation of colon multidrug resistance-associated protein 3 gene expression by bile acids
    Tanya C McCarthy
    Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada
    J Biol Chem 280:23232-42. 2005
    ..These data support a regulatory role for the VDR in the protection of colon cells from bile acid toxicity through regulation of the Mrp3 expression...
  69. ncbi Spontaneous development of liver tumors in the absence of the bile acid receptor farnesoid X receptor
    Fan Yang
    Department of Gene Regulation and Drug Discovery, Beckman Research Institute, City of Hope National Medical Center, 1500 E Duarte Road, Duarte, CA 91010, USA
    Cancer Res 67:863-7. 2007
    ..Our results suggest an intriguing link between metabolic regulation and hepatocarcinogenesis...
  70. ncbi Hepatobiliary transport of bile acids and organic anions
    Hajime Takikawa
    Department of Medicine, Teikyo University School of Medicine, Itabashi, Tokyo 173 8605, Japan
    J Hepatobiliary Pancreat Surg 9:443-7. 2002
    ..Farnesoid X receptor (FXR), which downregulates CYP7A1, the rate-limiting enzyme of bile acid biosynthesis, upregulates BSEP and downregulates NTCP. MRP2 is upregulated by both FXR and pregnane X receptor (PXR), which upregulates CYP3A...
  71. ncbi Bile-salt-mediated induction of antimicrobial and bile resistance in Salmonella typhimurium
    A M Prouty
    Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229 3900, USA
    Microbiology 150:775-83. 2004
    ..These data suggest that bile interacts with salmonellae to increase resistance to bile and other antimicrobials and that this can occur by marRAB- and acrAB-dependent pathways that function independently with respect to bile activation...
  72. pmc An in vitro study of the probiotic potential of a bile-salt-hydrolyzing Lactobacillus fermentum strain, and determination of its cholesterol-lowering properties
    Dora I A Pereira
    Food Microbial Sciences Unit, School of Food Biosciences, The University of Reading, Reading RG6 6BZ, United Kingdom
    Appl Environ Microbiol 69:4743-52. 2003
    ..The short-chain fatty acid concentrations, specifically the molar proportion of propionate and/or bile salt deconjugation, are probably the major mechanism involved in the purported cholesterol-lowering properties of this strain...
  73. ncbi High expression of the bile salt-homeostatic hormone fibroblast growth factor 19 in the liver of patients with extrahepatic cholestasis
    Frank G Schaap
    AMC Liver Center, Amsterdam, The Netherlands
    Hepatology 49:1228-35. 2009
    ....
  74. pmc The solute carrier family 10 (SLC10): beyond bile acid transport
    Tatiana Claro Da Silva
    Department of Pharmaceutical Sciences, University of Maryland, Baltimore, MD 21201, USA
    Mol Aspects Med 34:252-69. 2013
    ..The present mini-review provides a brief summary of recent progress on members of the SLC10 family...
  75. pmc An essential role for nuclear receptors SXR/PXR in detoxification of cholestatic bile acids
    W Xie
    Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA
    Proc Natl Acad Sci U S A 98:3375-80. 2001
    ..Therefore, we establish SXR and PXR as bile acid receptors and a role for the xenobiotic response in the detoxification of bile acids...
  76. ncbi The role of alpha1-fetoprotein transcription factor/LRH-1 in bile acid biosynthesis: a known nuclear receptor activator that can act as a suppressor of bile acid biosynthesis
    Antonio Del Castillo-Olivares
    Department of Biochemistry, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia 23298 0614, USA
    J Biol Chem 279:16813-21. 2004
    ....
  77. ncbi Role of nuclear receptors for bile acid metabolism, bile secretion, cholestasis, and gallstone disease
    Thierry Claudel
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University Graz, Austria
    Biochim Biophys Acta 1812:867-78. 2011
    ..Moreover, NRs may represent attractive drug targets for these disorders. This article is part of a Special Issue entitled: Translating nuclear receptors from health to disease...
  78. pmc Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia
    Michael Quante
    Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA
    Cancer Cell 21:36-51. 2012
    ..Our data suggest that BE and EAC arise from gastric progenitors due to a tumor-promoting IL-1β-IL-6 signaling cascade and Dll1-dependent Notch signaling...
  79. ncbi Functional variants of the central bile acid sensor FXR identified in intrahepatic cholestasis of pregnancy
    Saskia W C van Mil
    Maternal and Fetal Disease Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, England
    Gastroenterology 133:507-16. 2007
    ..It can cause premature delivery and intrauterine death. Bile acid synthesis, metabolism, and transport are regulated by the bile acid sensor FXR, and we hypothesized that genetic variation in FXR confers susceptibility to ICP...
  80. pmc Genetic characterization of the bile salt response in Lactobacillus plantarum and analysis of responsive promoters in vitro and in situ in the gastrointestinal tract
    Peter A Bron
    Wageningen Centre for Food Sciences, NIZO Food Research, P O Box 20, 6710 BA Ede, The Netherlands
    J Bacteriol 186:7829-35. 2004
    ....
  81. ncbi Effect of bile acid sequestrants on glucose metabolism, hepatic de novo lipogenesis, and cholesterol and bile acid kinetics in type 2 diabetes: a randomised controlled study
    C Beysen
    KineMed, Inc, 5980 Horton Street Suite 470, Emeryville, CA 94608, USA
    Diabetologia 55:432-42. 2012
    ....
  82. pmc Adaptation and preadaptation of Salmonella enterica to Bile
    Sara B Hernández
    Departamento de Genetica, Universidad de Sevilla, Sevilla, Spain
    PLoS Genet 8:e1002459. 2012
    ..This phenomenon underscores the existence of phenotypic heterogeneity in clonal populations of bacteria and may illustrate the adaptive value of gene expression fluctuations...
  83. pmc Hepatic free cholesterol accumulates in obese, diabetic mice and causes nonalcoholic steatohepatitis
    Derrick M Van Rooyen
    Liver Research Group, ANU Medical School at the Canberra Hospital, Garran, ACT, Australia
    Gastroenterology 141:1393-403, 1403.e1-5. 2011
    ..We investigated the basis for hepatic cholesterol accumulation with insulin resistance and its relevance to the pathogenesis of NASH...
  84. ncbi Fibrates modify the expression of key factors involved in bile-acid synthesis and biliary-lipid secretion in gallstone patients
    Nuria Roglans
    Pharmacology Unit, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain
    Eur J Clin Pharmacol 59:855-61. 2004
    ....
  85. pmc Hepatic insulin resistance directly promotes formation of cholesterol gallstones
    Sudha B Biddinger
    Research Division, Joslin Diabetes Center, 1 Joslin Place, Boston, Massachusetts 02215, USA
    Nat Med 14:778-82. 2008
    ..As a result, after twelve weeks on a lithogenic diet, all of the LIRKO mice develop gallstones. Thus, hepatic insulin resistance provides a crucial link between the metabolic syndrome and increased cholesterol gallstone susceptibility...
  86. pmc Bile acids promote the expression of hepatitis C virus in replicon-harboring cells
    Kyeong Ok Chang
    Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Avenue, Manhattan, KS 66506, USA
    J Virol 81:9633-40. 2007
    ..Our finding may also contribute to the establishment of better regimens for treatment of chronic HCV infections by including agents altering the bile acid-mediated FXR pathway...
  87. ncbi Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine
    Insook Kim
    Laboratory of Metabolism, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Lipid Res 48:2664-72. 2007
    ..These data provide evidence that FXR-mediated repression of bile acid synthesis requires the complementary actions of FXR in both liver and intestine and reveal mechanistic differences in feedback repression of CYP7A1 and CYP8B1...
  88. ncbi Bile salts induce expression of the afimbrial LDA adhesin of atypical enteropathogenic Escherichia coli
    Alfredo G Torres
    Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA
    Cell Microbiol 9:1039-49. 2007
    ..We concluded that bile salts increase expression of LDA, conferring a diffuse adherence pattern and having an impact on the adhesion properties of this aEPEC strain...
  89. ncbi Selective activation of nuclear bile acid receptor FXR in the intestine protects mice against cholestasis
    Salvatore Modica
    Laboratory of Lipid Metabolism and Cancer, Department of Translational Pharmacology, Consorzio Mario Negri Sud, Santa Maria Imbaro, Italy
    Gastroenterology 142:355-65.e1-4. 2012
    ..We investigated the role of activation of intestine-specific FXR in reducing hepatic levels of BAs and protecting the liver from cholestasis in mice...
  90. ncbi Lipid lowering with thyroid hormone and thyromimetics
    Bo Angelin
    Metabolism Unit, Department of Endocrinology, Karolinska Institutet at Karolinska University Hospital Huddinge, Stockholm, Sweden
    Curr Opin Lipidol 21:499-506. 2010
    ....
  91. ncbi Alterations in lipid metabolism mediate inflammation, fibrosis, and proliferation in a mouse model of chronic cholestatic liver injury
    Tarek Moustafa
    Laboratory of Experimental and Molecular Hepatology, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
    Gastroenterology 142:140-151.e12. 2012
    ..The liver controls central processes of lipid and bile acid homeostasis. We aimed to investigate whether alterations in lipid metabolism contribute to the pathogenesis of chronic cholestatic liver disease in mice...
  92. ncbi Taurolithocholic acid exerts cholestatic effects via phosphatidylinositol 3-kinase-dependent mechanisms in perfused rat livers and rat hepatocyte couplets
    Ulrich Beuers
    Department of Medicine II Grosshadern, Klinikum of the University of Munich, 81377 Munich, Germany
    J Biol Chem 278:17810-8. 2003
    ..These data strongly suggest that TLCA exerts cholestatic effects by PI3K- and PKCepsilon-dependent mechanisms that are reversed by tauroursodeoxycholic acid in a PI3K-independent way...
  93. pmc Diurnal variations of mouse plasma and hepatic bile acid concentrations as well as expression of biosynthetic enzymes and transporters
    Yu Kun Jennifer Zhang
    Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, United States of America
    PLoS ONE 6:e16683. 2011
    ..Recently, BAs have been recognized as signaling molecules beyond their well-established roles in dietary lipid absorption and cholesterol homeostasis...
  94. pmc Endocrine and paracrine role of bile acids
    Verena Keitel
    Clinic of Gastroenterology, Hepatology and Infectiology, Heinrich Heine University, Moorenstrasse 5, Dusseldorf D 40225, Germany
    World J Gastroenterol 14:5620-9. 2008
    ..Bile acid functions are mediated through different pathways which comprise the activation of nuclear hormone receptors, of intracellular kinases and of the plasma membrane-bound, G-protein coupled bile acid receptor TGR5/Gpbar-1...
  95. pmc Molecular mechanisms underlying bile acid-stimulated glucagon-like peptide-1 secretion
    H E Parker
    Cambridge Institute for Medical Research, Wellcome Trust MRC Building, Addenbrooke s Hospital, Cambridge, UK
    Br J Pharmacol 165:414-23. 2012
    ..The aim of the present study was to further our understanding of the bile acid receptor GPBA (TGR5), an L-cell target currently under therapeutic exploration...
  96. pmc Bile acids regulate cardiovascular function
    Sandeep Khurana
    Division of Gastroenterology and Hepatology, VA Maryland Health Care System and University of Maryland School of Medicine, Baltimore, MD, USA
    Clin Transl Sci 4:210-8. 2011
    ..This review focuses on BAs as newly recognized signaling molecules that modulate cardiovascular function...
  97. pmc Bile acid-induced arrhythmia is mediated by muscarinic M2 receptors in neonatal rat cardiomyocytes
    Siti H Sheikh Abdul Kadir
    National Heart and Lung Institute, Imperial College London, London, United Kingdom
    PLoS ONE 5:e9689. 2010
    ..We aim to investigate the mechanism of bile-acid induced arrhythmogenic effects in an in-vitro model of the fetal heart...
  98. ncbi Activation of the interleukin-6/STAT3 antiapoptotic pathway in esophageal cells by bile acids and low pH: relevance to barrett's esophagus
    Katerina Dvorak
    Department of Cell Biology and Anatomy, College of Medicine, The University of Arizona, Tucson, Arizona 85724, USA
    Clin Cancer Res 13:5305-13. 2007
    ..Here, we test the hypothesis that bile acids and gastric acids, two components of refluxate associated with gastresophageal reflux disease, activate the IL-6/STAT3 pathway...
  99. ncbi Cellular regulation of hepatic bile acid transport in health and cholestasis
    M Sawkat Anwer
    Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, 200 Westboro Road, N Grafton, MA 01536, USA
    Hepatology 39:581-90. 2004
  100. ncbi The farnesoid X receptor induces very low density lipoprotein receptor gene expression
    Audrey Sirvent
    GENFIT, Parc Eurasante, Loos, France
    FEBS Lett 566:173-7. 2004
    ....
  101. ncbi Regulation of bile acid synthesis: pathways, nuclear receptors, and mechanisms
    John Y L Chiang
    Department of Biochemistry and Molecular Pathology, Northeastern Ohio Universities College of Medicine, 4209 State Route 44, P O Box 95, Rootstown, OH 44272, USA
    J Hepatol 40:539-51. 2004

Research Grants75

  1. Bile acid-induced colon cancer cell proliferation
    Jean Pierre Raufman; Fiscal Year: 2009
    ..3c) The mechanism whereby bile acids activate metalloproteases will be determined by exploring the roles of PKC, Ca2+, and Src in bile acid-induced HB-EGF release. ..
  2. Mice Humanized with Hepatocytes and iPS Cells from Patients with Metabolic Diseas
    Stephen C Strom; Fiscal Year: 2010
    ..We propose these humanized mice will be a technology platform to better understand the human disease and it will aid in the development of gene or cellular therapy to correct these devastating diseases. ..
  3. Regulation of Bile Acid Synthesis by Nuclear Receptors
    John Y L Chiang; Fiscal Year: 2013
    ..The long-term objectives of this research are to elucidate the molecular mechanism of regulation of CYP7A1 and bile acid metabolism, and pathogenesis and treatment of metabolic diseases such as fatty liver disease, diabetes and obesity. ..
  4. Regulation of Hepatic SphK2 by Bile Acids: Effects on Lipid Metabolism
    HUIPING ROSE ZHOU; Fiscal Year: 2013
    ..Also, this study has potential impact on the identification and development of novel therapeutic targets for effective treatment of NAFLD and other related metabolic diseases. ..
  5. Surgical amelioration of type 2 diabetes: Hormones, microbiota and mitochondria
    PETER J contact HAVEL; Fiscal Year: 2010
    ..The contributions of alterations in the production of gastrointestinal and adipocyte hormones, changes of bile acids and intestinal microbial composition, as well as mitochondrial function will be assessed. ..
  6. Microsomal Cytochromes P450 and their Interactions with their Redox Partners
    Lucy A Waskell; Fiscal Year: 2013
    ....
  7. NPC1L1 and Metabolic Diseases
    Liqing Yu; Fiscal Year: 2013
    ..Given that NPC1L1 is the target of ezetimibe, an FDA-approved intestinal cholesterol absorption inhibitor that is widely used to lower blood cholesterol in humans, these studies have enormous translational potential. ..
  8. Dietary Cholesterol and Defects in Cholesterol Synthesis
    ROBERT DAVID STEINER; Fiscal Year: 2013
    ..Together, the in vivo and in vitro studies proposed should shed light on the pathogenesis of SLOS, and offer insights into treatment that to date have eluded investigators. ..
  9. Excessive Copper Levels Disrupt Hepatic Nuclear Receptor Function
    Clavia Ruth Wooton-Kee; Fiscal Year: 2011
    ..This research specifically addresses the biological mechanisms relevant to human liver pathology and to Wilson's disease. ..
  10. New pathways regulating bile acid homeostasis and cholestatic liver diseases
    Li Wang; Fiscal Year: 2013
    ..Fully defining the regulation of bile acid metabolism, including bile acid synthesis and catabolism, is essential for further advances in diagnosis, management, and prevention of cholestatic liver diseases. ..
  11. Regulation of Bile Acid Synthesis by Nuclear Receptors in Vivo
    Gregorio Gil; Fiscal Year: 2012
    ..The successful completion of this study will provide us with new insights into the molecular mechanisms involved in the regulation of bile acid biosynthesis. ..
  12. Colorado Center for Childhood Liver Disease Research and Education
    Ronald J Sokol; Fiscal Year: 2013
    ..We will also train the researchers of the future who will study these rare diseases. ..
  13. The Pittsburgh Cholestatic Liver Disease Consortium
    Benjamin L Shneider; Fiscal Year: 2013
    ..The Pittsburgh Cholestatic Liver Disease Consortium at Children's Hospital of Pittsburgh is ideally suited to participate in these prospective investigations. ..
  14. Breakthroughs to advance the in vitro propagation of human noroviruses
    Qiuhong Wang; Fiscal Year: 2010
    ..In vitro propagation of HuNoVs will provide the major breakthrough needed for development of new strategies and means to prevent and control HuNoV infections and thereby improve public health globally. ..
  15. The Role of Cyp2b in Toxicant Metabolism and Sensitivity
    William S Baldwin; Fiscal Year: 2012
    ....
  16. Thyroid-adrenergic synergism and adaptive thermogenesis
    Antonio C Bianco; Fiscal Year: 2013
    ..In particular, the finding of hepatic steatosis in D2KO animals offers a tantalizing hint of a previously unexpected role (whether direct or indirect) for D2 in the regulation of hepatic lipid homeostasis. ..
  17. Epigenetic regulation of liver transporters
    Frederick J Suchy; Fiscal Year: 2013
    ..These studies will provide insight into an unexplored area of hepatic biology and pathobiology, and suggest potential new targets for drug development. ..
  18. Functions of the Human OST-alpha and OST-beta Proteins
    Patricia M Hinkle; Fiscal Year: 2013
    ....
  19. CELLS PROCESSING HIGH DENSITY LIPOPROTEINS
    Salman Azhar; Fiscal Year: 2013
    ..Both bile acids and steroids are synthesized from SR-BI-mediated selectively delivered cholesterol, thus underscoring the relevance of understanding the cellular mechanisms controlling the functional expression of SR-BI. ..
  20. Crosstalk between estrogen and bile acid signaling pathway
    Ruitang Deng; Fiscal Year: 2013
    ..Understanding the mechanisms and pathological consequences will provide a molecular basis to develop new drugs to treat or prevent those diseases. ..
  21. USC Research Center for Liver Disease
    Neil Kaplowitz; Fiscal Year: 2013
    ....
  22. (PQA1) Mechanism of Vitamin D Chemoprevention Against Colon Cancer
    Yan Chun Li; Fiscal Year: 2013
    ..These studies will greatly advance our understanding of chemopreventive mechanisms of VD against colon cancer. ..
  23. Participation in Cytochrome b5 in Anesthetic Metabolism
    Lucy A Waskell; Fiscal Year: 2010
    ....
  24. Regulation of cholesterol catabolism by bile acids
    Jongsook Kim Kemper; Fiscal Year: 2013
    ..These studies will elucidate how SHP epigenetically controls BA-regulated hepatic functions, and identify novel potential diagnostic and/or therapeutic targets for metabolic diseases. ..
  25. Structural Biology of the Apical Bile Acid Transporter.
    Peter W Swaan; Fiscal Year: 2012
    ....
  26. Structure/Function of Steroid Transforming AKR's
    Trevor M Penning; Fiscal Year: 2011
    ..This application will establish whether these genetic changes result in abnormal bile-acid production and are causal in these deficiencies. ..
  27. MOLECULAR BIOLOGY OF BILE ACID SYNTHESIS
    JOHN CHIANG; Fiscal Year: 2009
    ..Drugs targeting to nuclear receptor and signaling pathways, and miRNA antagomirs may be developed for treating metabolic liver diseases. ..
  28. Regulation of Hepatic Metabolic Function by Parenteral Nutrition
    Douglas G Burrin; Fiscal Year: 2013
    ..These studies in premature pigs are highly translational and will lead to new clinical practices in nutritional support and prevention of liver disease in infants. ..
  29. Bile Acids, Genetic Control and Colonic Function in Irritable Bowel Syndrome
    MICHAEL L CAMILLERI; Fiscal Year: 2013
    ....
  30. Novel STIM1-dependent cyclic AMP signaling pathway in colonic epithelial function
    Aldebaran M Hofer; Fiscal Year: 2013
    ....
  31. FUNCTIONAL ANALYSIS OF NUCLEAR RECEPTOR VARIANTS
    Curtis J Omiecinski; Fiscal Year: 2013
    ....
  32. MOLECULAR BIOLOGY OF BILE ACID SYNTHESIS
    John Y L Chiang; Fiscal Year: 2013
    ..Drugs targeting to nuclear receptor and signaling pathways, and miRNA antagomirs may be developed for treating metabolic liver diseases. ..
  33. Effects of sleep deprivation and high fat diet on human CYP7A1 circadian rhythm
    JESSICA MARIE FERRELL; Fiscal Year: 2013
    ..The proposed studies aim to understand the contribution of deregulated circadian liver metabolism in the progression of diabetes and obesity. ..
  34. Regulation of Hepatic Uptake of Endogenous Signaling Molecules and Xenobiotics
    Ivan Csanaky; Fiscal Year: 2013
    ....
  35. Control of cAMP Mediated Glucagon Response by Bile Acids
    Norman H Lee; Fiscal Year: 2011
    ..The knowledge gained from these studies could in turn impact both the diagnosis and treatment of cholestatic hepatobiliary disorders, as well as diabetes. ..
  36. Function and regulation of OATP1B1 and OATP1B3
    Wei Yue; Fiscal Year: 2013
    ..The outcomes of these experiments will greatly broaden our ability to predict and prevent transport-mediated drug-drug interactions. ..
  37. Characterization of TGR5-D2-WSB1 signaling in metabolic homeostasis in vivo
    ANTONIO C contact BIANCO; Fiscal Year: 2010
    ..2. Tissue-specific TGR5 and WSB1 expression is critical in metabolic control. 3. Signaling through the TGR5-D2-WSB1 pathway affects cellular metabolic profile and gene expression profiles. ..
  38. Xenobiotic sensors PXR and CAR and regulation of the UGT1 locus
    Robert H Tukey; Fiscal Year: 2012
    ..This application is the first attempt to investigate how human UGTs are regulated in mice, and to apply this animal to understand the impact of glucuronidation towards drug-drug interactions, drug metabolism and eventually disease. ..
  39. Role of Bile Acids and Gut Bacteria in GI Diseases
    Phillip B Hylemon; Fiscal Year: 2013
    ..abstract_text> ..
  40. Interplay between metabolism and FXR activation in scoparone signaling
    Bingfang Yan; Fiscal Year: 2013
    ..Interestingly, scoparone has been found to exert these very activities. Thus, a confirmation on the functional connection between FXR and scoparone will have broad mechanistic and therapeutic implications. ..
  41. Shifts in the Gastrointestinal Metabolome During Clostridium difficile Infection
    CASEY THERIOT; Fiscal Year: 2013
    ..abstract_text> ..
  42. Regulation of Metabolism by the Hormone FGF15/19
    Steven A Kliewer; Fiscal Year: 2013
    ..Insights from these studies may provide new clinical strategies for treating obesity, diabetes, and other forms of metabolic disease. ..
  43. Dissecting mechanisms by which GI surgery delays diabetes onset in UCD-T2DM rats
    Peter J Havel; Fiscal Year: 2013
    ..New therapeutic targets will be pursued by performing microarray analysis of enteroendocrine cells isolated via laser capture dissection from selected gut segments and analyzing gut microbial populations by pyrosequencing. ..
  44. Functional studies of PGRMC1 in cholesterol homeostasis
    PETER JOHN ESPENSHADE; Fiscal Year: 2010
    ....
  45. Trafficking mechanisms for secretory vesicles in pancreatic duct epithelial cells
    Duk Su Koh; Fiscal Year: 2013
    ..The experiments are broadly relevant to treatment of disorders of the digestive system. ..
  46. Role of Bile Acids in the Initiation of Liver Regeneration
    Willscott E Naugler; Fiscal Year: 2013
    ....
  47. Metabolic control of hepatitis B virus (HBV) biosynthesis: role of FXR and SHP
    VANESSA CURRAGH REESE; Fiscal Year: 2010
    ..25-1 million deaths/year in the world from HBV mediated hepatocellular carcinoma. Determining if HBV is a metabolic gene that can be nutritionally regulated, could greatly impact the affliction of hepatitis B on public health. ..
  48. Hepatic Cholesteryl Ester Metabolism and Cholesterol Elimination
    Shobha Ghosh; Fiscal Year: 2013
    ..Aim 4: To obtain in vivo "proof of concept" by liver-specific targeted disruption of CEH in mice and to determine its effect on intracellular CE metabolism and atherosclerosis. ..
  49. NSAID-Phosphatidylcholine Association: Insight in GI Ulcer Pathogenesis/Therapy
    Lenard M Lichtenberger; Fiscal Year: 2010
    ..Furthermore, by pre-associating soy PC with NSAIDs we have developed a novel family GI-safer, therapeutically effective PC-NSAIDs that can be made available to the public using an accelerated FDA regulatory pathway. ..
  50. Gut bile acids, Fxr, &Fgf15 in total parenteral nutrition-associated cholestasis
    Grace L Guo; Fiscal Year: 2013
    ....
  51. Cholesterol Ester Hydrolysis and Cholesterol Efflux
    Shobha Ghosh; Fiscal Year: 2012
    ..Given the prevalence of atherosclerosis and coronary artery disease with obesity and insulin resistance as major risk factors, the current findings are likely to have important clinical relevance. ..
  52. The role of PGRMC1 in hepatic cholesterol homeostasis
    RITA THOMAS BROOKHEART; Fiscal Year: 2013
    ....
  53. Development of ROR ligands for treatment of metabolic diseases
    Thomas P Burris; Fiscal Year: 2010
    ..RELEVANCE: Our proposed studies to develop ROR targeted drugs may provide the basis for novel therapeutics targeting the RORs for treatment of metabolic disorders such as diabetes, atherosclerosis and obesity. ..
  54. Regulation of Intestinal Bile Acid Transport
    Waddah A Alrefai; Fiscal Year: 2013
    ....
  55. Regulation of REV-ERBalpha and REV-ERBbeta function of HEME
    Thomas P Burris; Fiscal Year: 2012
    ..abstract_text> ..
  56. The Role of IL-6/STAT3 in the Pathogenesis and Progression of Barrett's Esophagus
    Ronnie Fass; Fiscal Year: 2012
    ..abstract_text> ..
  57. Carboxyl Ester Lipase Affects Hepatic HDL Metabolism
    PHILIP HOWLES; Fiscal Year: 2009
    ....
  58. Mechanisms of Vascular Dysfunction in Cirrhosis
    Sandeep Khurana; Fiscal Year: 2012
    ..This line of investigation will fill critical gaps in understanding the mechanisms of vascular dysfunction in cirrhosis and identify molecules for therapeutic targeting. ..
  59. Dysregulated Hypothalamic-pituitary-adrenal Axis During Biliary Hyperplasia
    Sharon Demorrow; Fiscal Year: 2013
    ..This knowledge may play a paramount role in the development of therapeutic strategies for the treatment of cholangiopathies. ..
  60. Coordination of gut-liver bile acid signaling by FXR
    Jongsook Kim Kemper; Fiscal Year: 2013
    ..Our proposed studies should provide new insights into the mechanisms by which FXR coordinates gut-liver bile acid signaling and may reveal novel therapeutic targets to treat metabolic disorders. ..
  61. Metabolic and xenobiotic control of thyroid hormone metabolism
    Antonio C Bianco; Fiscal Year: 2013
    ....
  62. Hepatic Fatty Acid Metabolism and Steatosis
    NICHOLAS DAVIDSON; Fiscal Year: 2013
    ..abstract_text> ..
  63. The Perinatal Pharmacology of the Nuclear Receptor
    Wen Xie; Fiscal Year: 2013
    ..This applicant agrees and has requested funds to participate in the annual NIH-sponsored two-day meetings focusing on Developmental Pharmacology in Bethesda, MD. This applicant also agrees to cooperate with other investigators. ..
  64. REGULATION OF BILE ACID SYNTHESIS
    JOHN CHIANG; Fiscal Year: 1999
    ....
  65. INTRACELLULAR TRANSPORT OF AMPHIPATHS
    Bruce Luxon; Fiscal Year: 2000
    ..Insights and new methods developed in this proposal may apply to the intracellular transport of other biologically important molecules including cholesterol, thyroid and steroid hormones. ..
  66. EFFECTS OF BILE ACIDS ON CALCIUM AND IRON ABSORPTION
    Edward Moore; Fiscal Year: 1990
    ..Studies are also proposed to determine possible enhancement of ileal Ca++, Fe++ and Fe++ absorption by bile salt transport...
  67. MEMBRANE DYNAMICS AND STEROL BIOSYNTHESIS IN YEAST
    Robin Wright; Fiscal Year: 1999
    ..This information has medical significance for understanding the regulation of cholesterol synthesis and may also uncover novel approaches for clinical therapies aimed at controlling cholesterol biosynthesis in vivo. ..
  68. URSODIOL-METHOTREXATE FOR PRIMARY BILIARY CIRRHOSIS
    Burton Combes; Fiscal Year: 2003
    ..The safety of each therapeutic regimen is also being determined. ..
  69. Calcium Signaling in Developing Intestinal Epithelium
    Mrinalini Rao; Fiscal Year: 2005
    ....
  70. NUTRITIONAL INFLUENCES ON COLON CANCER IN THE TAMARIN
    Lynne Ausman; Fiscal Year: 1991
    ..Results from these studies will determine whether the concentrations and/or patterns of the measured parameters are affected by animal species and by dietary fat...
  71. EFFECT OF VITAMIN E ON HEPATOCYTE STRUCTURE AND FUNCTION
    Ronald Sokol; Fiscal Year: 1991
    ..Furthermore, a better understanding of the physiologic role of vitamin E in cellular membrane function will be achieved through these proposed studies...
  72. HEPATIC DRUG ELIMINATION IN PREGNANCY
    Mary Vore; Fiscal Year: 2010
    ..abstract_text> ..
  73. HEPATIC DRUG ELIMINATION IN PREGNANCY
    Mary Vore; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
  74. BILE ACIDS AND HEPATOCELLULAR SIGNAL TRANSDUCTION
    Bernard Bouscarel; Fiscal Year: 1999
    ....
  75. Function and Regulatin of Intestinal Basolateral Organic Solute Transporters
    Anuradha Rao; Fiscal Year: 2009
    ....